TY - JOUR. T1 - Memantine selectively blocks extrasynaptic NMDA receptors in rat substantia nigra dopamine neurons. AU - Wu, Yan Na. AU - Johnson, Steven W.. N1 - Funding Information: This study was supported by a Veterans Affairs Merit (0383) Grant (SWJ) and by the Parkinson׳s Disease Research, Education and Clinical Center at Veterans Affairs Portland Health Care System .. PY - 2015/4/7. Y1 - 2015/4/7. N2 - Recent studies suggest that selective block of extrasynaptic N-methyl-d-aspartate (NMDA) receptors might protect against neurodegeneration. We recorded whole-cell currents with patch pipettes to characterize the ability of memantine, a low-affinity NMDA channel blocker, to block synaptic and extrasynaptic NMDA receptors in substantia nigra zona compacta (SNC) dopamine neurons in slices of rat brain. Pharmacologically isolated NMDA receptor-mediated EPSCs were evoked by electrical stimulation, whereas synaptic and extrasynaptic receptors were activated by superfusing the slice with NMDA (10 ...

I am very impressed with the recent article by Whittington et al. , which demonstrated that dexmedetomidine increased the cocaine-induced seizure threshold via the attenuation of the cocaine-induced increase in extracellular dopamine concentration in the rat nucleus accumbens. 1It is true that the increase in extracellular dopamine concentration in the nucleus accumbens may be closely related to the cocaine-induced seizure activity because cocaine inhibits dopamine transporters, but recent studies have suggested that ς receptors, which are endoplasmic reticulum protein and directly activated by cocaine, are more likely involved in the cocaine-induced seizure activity than the dopamine transporters. 2On the other hand, we have recently demonstrated that ketamine, which has anticonvulsant and also proconvulsant properties, markedly increases dopamine release in the nucleus accumbens. 3Ketamine affected the ς receptors 4and ketamine-induced c-fos protein expression in the posterior cingulate and ...

TY - JOUR. T1 - Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization. AU - Wolf, Marina. AU - White, F. J.. AU - Nassar, R.. AU - Brooderson, R. J.. AU - Khansa, M. R.. PY - 1993/1/1. Y1 - 1993/1/1. N2 - Various changes in the function of dopamine neurons have been proposed to underly the development of behavioral sensitization to the locomotor stimulant effects of d-amphetamine. The present study examined the relative importance of two such mechanisms after both short (3-4 days off) and longer (10-14 days off) withdrawals from repeated amphetamine or saline injection (1 mg/kg/day, days 1-5 and 8-12). First, single-unit recording was used to examine the sensitivity of impulse-regulating somatodendritic autoreceptors located on mesoaccumbens dopamine neurons in the rat ventral tegmental area. Second, in vivo microdialysis was used to examine the ability of amphetamine challenge to increase extracellular dopamine levels in the rat ...

In membrane preparations from rat striatum, where adenosine A2A and dopamine D2 receptors are coexpressed, stimulation of adenosine A2A receptors was found to decrease the affinity of dopamine D2 receptors for dopamine agonists. We now demonstrate the existence of this antagonistic interaction in a fibroblast cell line (Ltk-) stably transfected with the human dopamine D2 (long-form) receptor and the dog adenosine A2A receptor cDNAs (A2A-D2 cells). In A2A-D2 cells, but not in control cells only containing dopamine D2 receptors (D2 cells), the selective adenosine A2A agonist 2-[p-(2-carboxyethyl)-phenethylamino]-5-N-ethyl-carboxamido adenosine (CGS 21680) induced a 2-3-fold decrease in the affinity of dopamine D2 receptors for dopamine, as shown in competition experiments with dopamine versus the selective dopamine D2 antagonist [3H]raclopride. By contrast, activation of the constitutively expressed adenosine A2B receptors with 5-N-ethyl-carboxamidoadenosine (NECA) did not modify dopamine D2 ...

Dopamine is a classic central neurotransmitter, which is synthesized by dopaminergic neurons and stored in vesicles, and may be released from neurons by cell cleavage. Dopamine acts on the dopamine receptor, and changes the cell membrane on the ion permeability through a series of reactions, resulting in physiological effects. Dopamine has the effect of regulating physical activity, mental activity, endocrine and cardiovascular activity. Dopaminergic neuronal lesions can lead to a variety of diseases, such as Parkinsons disease, schizophrenia and so on.. By the fifties, dopamine had been thought to be a precursor of synthetic norepinephrine. A team of pioneering studies confirmed that dopamine was an important neurotransmitter in the brain and that there was a close relationship with Parkinsons disease. Since then, scientists had conducted a lot of researches on dopamine, and people had deepen understanding on such magical small molecules.. It is now generally accepted that dopamine receptors ...

Many connections in the basal ganglia are made around birth when animals are exposed to a host of new affective, cognitive, and sensori-motor stimuli. It is thought that dopamine modulates cortico-striatal synapses that result in the strengthening of those connections that lead to desired outcomes. We propose that there must be a time before which stimuli cannot be processed into functional connections, otherwise it would imply an effective link between stimulus, response, and reward in uterus. Consistent with these ideas, we present evidence that early in development dopamine neurons are electrically immature and do not produce high-frequency firing in response to salient stimuli. We ask first, what makes dopamine neurons immature? and second, what are the implications of this immaturity for the basal ganglia? As an answer to the first question, we find that at birth the outward current is small (3nS-V), insensitive to Ca2z, TEA, BK, and SK blockers. Rapidly after birth, the outward current ...

Dopaminergic means related to dopamine (literally, working on dopamine), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain structures facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic. Enzymes that regulate the biosynthesis or metabolism of dopamine such as aromatic L-amino acid decarboxylase or DOPA decarboxylase, monoamine oxidase (MAO), and catechol O-methyl transferase (COMT) may be referred to as dopaminergic as well. Also, any endogenous or exogenous chemical substance that acts to affect dopamine receptors or dopamine release through indirect actions (for example, on neurons that synapse onto neurons that ...

The localization of dopamine stores and the expression and localization of dopamine (DAT) and vesicular monoamine transporters (VMAT) type-1 and -2 and of dopamine D1-like and D2-like receptor subtypes were investigated in rat submandibular, sublingual, and parotid salivary glands by HPLC with electrochemical detection, as well as immunochemical and immunohistochemical techniques. Male Wistar rats of 2 mo of age were used. The highest dopamine levels were measured in the parotid gland, followed by the submandibular and sublingual glands. Western blot analysis revealed DAT, VMAT-1, VMAT-2, and dopamine receptors immunoreactivity in membrane preparations obtained from the three glands investigated. Immunostaining for dopamine and transporters was developed within striated ducts. Salivary glands processed for dopamine receptors immunohistochemistry developed an immunoreaction primarily in striated and excretory ducts. In the submandibular gland, acinar cells displayed strong immunoreactivity for ...

Converging evidence from clinical, preclinical, neuroimaging, and genetic research implicates dopamine neurotransmission in the pathophysiology of attention deficit hyperactivity disorder (ADHD). The in vivo neuroreceptor imaging evidence also suggests alterations in the dopamine system in ADHD; however, the nature and behavioral significance of those have not yet been established. Here, we investigated striatal dopaminergic function in ADHD using [(11)C]raclopride PET with a d-amphetamine challenge. We also examined the relationship of striatal dopamine responses to ADHD symptoms and neurocognitive function. A total of 15 treatment-free, noncomorbid adult males with ADHD (age: 29.87 ± 8.65) and 18 healthy male controls (age: 25.44 ± 6.77) underwent two PET scans: one following a lactose placebo and the other following d-amphetamine (0.3 mg/kg, p.o.), administered double blind and in random order counterbalanced across groups. In a separate session without a drug, participants performed a ...

Cocaine abuse is a serious health problem in many areas of the world, yet there are no proven effective medications for the treatment of cocaine dependence.Preclinical studies suggest that the reinforcing effect of cocaine that promotes its abuse is mediated by blockade of the presynaptic dopamine transporter. This results in increased dopamine activity in the mesolimbic or meso-accumbens dopamine reward system of brain. Development of new medications to treat cocaine dependence has focused on manipulation of this dopamine system, either by direct action on dopamine binding sites (transporter or receptors) or indirectly by affecting other neurotransmitter systems that modulate the dopamine system. In principle, a medication could act via one of three mechanisms: (i) as a substitute for cocaine by producing similar dopamine effects; (ii) as a cocaine antagonist by blocking the binding of cocaine to the dopamine transporter; or (iii) as a modulator of cocaine effects by acting at other than the ...

Gambling disorder sufferers prefer immediately larger rewards despite long term losses on the Iowa Gambling Task (IGT), and these impairments are associated with dopamine dysfunctions. Dopamine is a neurotransmitter linked with temporal and structural dysfunctions in substance use disorder, which has supported the idea of impaired decision-making and dopamine dysfunctions in gambling disorder. However, evidence from substance use disorders cannot be directly transferred to gambling disorder. This article focuses on three hypotheses of dopamine dysfunctions in gambling disorder, which appear to be fallacies, i.e., have not been supported in a series of positron emission tomography (PET) studies. The first fallacy suggests that gambling disorder sufferers have lower dopamine receptor availability, as seen in substance use disorders. However, no evidence supported this hypothesis. The second fallacy suggests that maladaptive decision-making in gambling disorder is associated with higher ...

The mesocorticolimbic dopamine system is essential for cognitive and emotive brain functions and is thus an important target in major brain diseases like schizophrenia, drug addiction, and attention deficit hyperactivity disorder. However, the cellular basis for the diversity in behavioral functions …

Dopamine D1-D5 receptor protein immunoreactivity was investigated in different sized pial, renal and mesenteric artery branches using immunohistochemical techniques and anti-dopamine D1-D5 receptor protein antibodies. Faint dopamine D1 receptor protein immunoreactivity was observed in smooth muscle of tunica media of pial, renal and mesenteric artery branches. Dopamine D2 receptor protein immunoreactivity was located in the adventitia and adventitia-media border of pial and renal artery branches and to a lesser extent of mesenteric artery branches. No dopamine D3 receptor protein immunoreactivity was observed in pial and mesenteric arteries. In renal arteries a moderate dopamine D3 receptor immunoreactivity was detectable in the adventitia and adventitia-media border. A strong dopamine D4 receptor protein immunoreactivity displaying the same localization of dopamine D2 receptor protein was observed in pial and mesenteric arteries, but not in renal artery branches. Moderate dopamine D5 receptor ...

TY - JOUR. T1 - A site-specific mutation of tyrosine hydroxylase reduces feedback inhibition by dopamine in genetically modified cells grafted in parkinsonian rats. AU - Chang, J. W.. AU - Lee, W. Y.. AU - Milstien, S.. AU - Kang, U. J.. PY - 2002/10. Y1 - 2002/10. N2 - Aromatic L-amino acid decarboxylase (AADC) is necessary for conversion of L-DOPA to dopamine. Therefore, AADC gene therapy has been proposed to enhance pharmacological or gene therapies delivering L-DOPA. However, addition of AADC to the grafts of genetically modified cells expressing tyrosine hydroxylase (TH) and GTP cyclohydrolase 1 (GCH1), which produce L-DOPA in parkinsonian rats, resulted in decreased production of L-DOPA and dopamine owing to feedback inhibition of TH by dopamine. End-product feedback inhibition has been shown to be mediated by the regulatory domain of TH, and site-specific mutation of serine 40 makes TH less susceptible to dopamine inhibition. Therefore, we investigated the efficacy of using TH with serine ...

CiteWeb id: 19980000092. CiteWeb score: 5133. Schultz, Wolfram. Predictive reward signal of dopamine neurons. J. Neurophysiol. 80: 1-27, 1998. The effects of lesions, receptor blocking, electrical self-stimulation, and drugs of abuse suggest that midbrain dopamine systems are involved in processing reward information and learning approach behavior. Most dopamine neurons show phasic activations after primary liquid and food rewards and conditioned, reward-predicting visual and auditory stimuli. They show biphasic, activation-depression responses after stimuli that resemble reward-predicting stimuli or are novel or particularly salient. However, only few phasic activations follow aversive stimuli. Thus dopamine neurons label environmental stimuli with appetitive value, predict and detect rewards and signal alerting and motivating events. By failing to discriminate between different rewards, dopamine neurons appear to emit an alerting message about the surprising presence or absence of rewards. All ...

DOPAMINE. The Key to Increased Motivation and Focus in Children and Teens. Have you ever wondered why children and teens seem to be so addicted to their smart phones and other devices? Parents are frustrated with their childrens lack of attention and motivation but what do their devices have to do with this? The answer is found in science!. Often referred to as the motivator molecule, dopamine is a feel good chemical that is released in the brain which helps us focus and feel motivated. When dopamine levels are low, it can result in symptoms such as difficulty focusing, decreased motivation, trouble problem-solving, and social anxiety. Therefore, many ADHD medications target dopamine levels.. When children and teens have low dopamine levels, we often find that they spend more time on video games and smartphone apps, and some tend to be thrill seekers. These things give a boost of dopamine, which makes them feel good and then leads to them seeking out more of the same thing. This constant ...

The putamen of the human striatum is a heterogeneous nucleus that contains the primary site of loss of dopamine (DA) in Parkinsons disease (PD). Furthermore, different functional domains of the putamen are heterogeneously susceptible to DA loss, and yet the dynamic regulation of extracellular DA concentration ([DA](o)) and comparison between domains has not been explored in the primate brain. In these studies, DA was measured in real time using fast-scan cyclic voltammetry at a carbon-fiber microelectrode in vitro in striatal sections from the common marmoset (Callithrix jacchus). [DA](o) released by a single stimulus pulse varied threefold along a ventromedial-dorsolateral axis. DA uptake was via the DA transporter (GBR12909 sensitive, desipramine insensitive). On the basis of data modeling with simulations of Michaelis-Menten kinetics, rate maximum, V(max), varied with region: both [DA](o) and V(max) were greatest in regions most vulnerable in PD. These differences were reflected in part by regional

University Department of Psychiatry, Warneford Hospital, Oxford, UK. RATIONALE: Tyrosine depletion has been shown to reduce dopamine over activity in animal and human investigations. However, the effects on basal dopamine function have not been explored. Such information could establish tyrosine depletion as an effective probe of dopamine function in healthy volunteers and would also have relevance for future therapeutic applications of this manipulation.. OBJECTIVE: The present study investigated the effect of acute tyrosine depletion on dopamine function in healthy volunteers using a combination of neuroendocrine, neuropsychological and subjective measures.. METHODS: On one occasion, volunteers received an amino acid drink selectively lacking tyrosine and phenylalanine (TYR-free), whilst on the other they received a balanced (BAL) amino acid drink. Plasma prolactin, amino acid levels and subjective state were monitored over 6 h following the two drinks, and volunteers also completed a battery ...

Mucuna pruriens is an Ayurvedic herb that has been used for centuries to increase libido, energy, optimize blood sugar, mood support, and is well known for its powers as an adaptogen. Mucuna has been shown to increase the neurotransmitter dopamine, which is very important for optimal brain health. Optimal hormone production starts with brain health and optimal levels of dopamine are critical for brain health.. Dopamine is a powerhouse neurotransmitter that provides the boost you need to get out of bed in the morning and take charge of your day. It also plays a big role in sex drive and sexual function. Dopamine controls the sex hormone control center of the brain. Dopamine is also a powerful growth hormone booster and reduces levels of prolactin. Prolactin is a nasty hormone that lowers testosterone levels in men. According to anti-aging expert Dr. Eric Braverman, dopamine is intimately connected to addictive behavior. People with low dopamine levels are often addicted to sources of quick ...

There are several foods that boost serotonin levels, such as salmon, chicken, … Dopamine is important for many brain and body functions. Dopamine & norepinephrine are two critical neurotransmitters that regulate your mood and behavior. Medically reviewed by David Ozeri, MD What Is Lithium? Do whatever it takes to exercise and try to reach that runners high. Includes dopamine side effects, interactions and indications. So, what is it why does it make us feel so good? Dopamine plays an important role in controlling motor behavior, the emotional reward, and behavior motivation mechanisms. - Veronika Polozkova . The oral dopamine agonist bromocriptine also augmented GHRH-stimulated GH secretion. At the very least, a good diet or even restricting food intake can increase dopamine receptors [5]. Dopamine plays a part in controlling the movements a person makes, as well as their emotional responses. read non-fiction books, especially spiritual texts such as Peace Is Every Step enjoy nourishing ...

Title:Effects of Tetrahydroxystilbene Glucoside on Liver P450 Enzym e Expressions in Lipopolysaccharide-induced Dopamine Neuronal Dama ge Rats. VOLUME: 14 ISSUE: 8. Author(s):Guo-Qing Wang, Yan-Zhen Zhou, Jia-Wei Tian, Jing-Shan Shi, Jie Liu and Feng Zhang*. Affiliation:Key Lab of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, Department of Ear-Nose-Throat Surgery, the Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou 563000, Key Lab of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, Key Lab of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, Key Lab of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, Guizhou 563000, Key Lab of Basic Pharmacology of Ministry of Education, Zunyi Medical University, 201 Dalian Road, Zunyi, Guizhou 563000. Keywords:Tetrahydroxystilbene glucoside, rat liver, dopaminergic neuronal damage, ...

The cellular localization of DARPP-32, a dopamine- and cAMP-regulated phosphoprotein of Mr 32,000 that appears to mediate certain actions of dopamine in the mammalian brain by acting as an inhibitor of protein phosphatase 1, was studied in the kidney of several species. DARPP-32 mRNA and DARPP-32-like immunoreactivity were found in the cytoplasm of cells in the thick ascending limb of the loop of Henle. The specific dopamine DA1 agonist SKF 82526 caused a dose-dependent inhibition of Na+,K+-ATPase activity, which could be blocked by SCH 23390, a specific DA1 antagonist, and by PKI-(5-24) amide, a specific inhibitor of cAMP-dependent protein kinase. The results indicate that DA1 dopamine receptors and DARPP-32, an intracellular third messenger for dopamine, are part of the signal-transduction process for dopamine acting on renal tubule cells. ...

Tobacco products are some of the most commonly used psychoactive drugs worldwide. Besides nicotine, alkaloids in tobacco include cotinine, myosmine, and anatabine. Scientific investigation of these constituents and their contribution to tobacco dependence is less well developed than for nicotine. The present study evaluated the nucleus accumbens dopamine-releasing properties and rewarding and/or aversive properties of nicotine (0.2-0.8mg/kg), cotinine (0.5-5.0mg/kg), anatabine (0.5-5.0mg/kg), and myosmine (5.0-20.0mg/kg) through in vivo microdialysis and place conditioning, respectively, in adult and adolescent male rats. Nicotine increased dopamine release at both ages, and anatabine and myosmine increased dopamine release in adults, but not adolescents. The dopamine release results were not related to place conditioning, as nicotine and cotinine had no effect on place conditioning, whereas anatabine and myosmine produced aversion in both ages. While the nucleus accumbens shell is hypothesized to play

Prior work has shown that functional connectivity between the midbrain and putamen is altered in patients with impairments in the dopamine system. This study examines whether individual differences in midbrain-striatal connectivity are proportional to the integrity of the dopamine system in patients with nigrostriatal dopamine loss (Parkinsons disease and dementia with Lewy bodies). We assessed functional connectivity of the putamen during resting state fMRI and dopamine transporter (DAT) availability in the striatum using 11C-Altropane PET in twenty patients. In line with the hypothesis that functional connectivity between the midbrain and the putamen reflects the integrity of the dopaminergic neurotransmitter system, putamen-midbrain functional connectivity was significantly correlated with striatal DAT availability even after stringent control for effects of head motion. DAT availability did not relate to functional connectivity between the caudate and thalamus/prefrontal areas. As such, ...

PubMed journal article: Dissociation of prolactin secretion from tuberoinfundibular dopamine activity in late pregnant rats. Download Prime PubMed App to iPhone, iPad, or Android

The dopamine hypothesis of schizophrenia states that the illness is due to overactivity of dopamine mechanisms in the brain. This hypothesis is based on two facts: (1) drugs, such as amphetamine, that enhance dopaminergic neurotransmission in the brain, may occasionally provoke a schizophrenic psychosis; and (2) acute administration of neuroleptic drugs, which are used to treat schizophrenia and other psychotic illnesses, causes blockade of brain dopamine receptors and initiates a chain of compensatory events which attempt to overcome such an action. We have previously shown that administration of neuroleptic drugs to rats for up to 18 months produces unexpected effects1,2: after 6 months, all signs of blockade of dopamine receptors in the striatum have disappeared, and thereafter striatal dopamine receptors increase in number and become behaviourally supersensitive to administered dopamine agonists such as apomorphine. We now show that such chronic exposure to neuroleptics completely alters ...

Since the identification of a number of Parkinsons disease genes in humans, much effort has been spent at developing pre-clinical models of the disease. However, most genetic pre-clinical models have been disappointing because the mutations do not usually lead to the death of dopamine-containing neurons, as is seen in humans. However, these models may help to identify early symptoms of Parkinsons disease that appear prior to cell death. In the present project, our main goal will be to evaluate whether an early phenotype common to many Parkinsons disease genetic models is a perturbation of the function of the dopamine transporter, a protein that works to recycle dopamine after its release in the brain ...

This is a study of safinamide, an investigational drug for Parkinson disease (PD). Safinamide is being developed as add-on therapy for the treatment of Parkinson disease. It is theorized that safinamide acts by increasing the available dopamine in those areas of the brain where dopamine is decreased as a result of Parkinson;s Disease. . Dopamine in the brain is involved in controlling body movements. Safinamide has been extensively studied in animals, and has been shown to increase the level of dopamine in these animals. Safinamide has also been tested in patients with Parkinson disease. The goal of this research trial is to see if safinamide is safe and well tolerated and to better understand how it affects the dopamine system in the brain in individuals with Parkinson disease. Data from this trial may provide essential information about the effectiveness and safety of these doses of safinamide in patients with early Parkinson disease, who are already receiving a stable dose of their normal ...

The spontaneously hypertensive rat (SHR) has been proposed as an animal model for attention-deficit hyperactivity disorder (ADHD). The behavioural problems have been suggested to be secondary to altered reinforcement mechanisms in which nucleus accumbens dopaminergic activity plays an important role. Interaction between the noradrenergic and dopaminergic system in the nucleus accumbens has been implicated in the locomotor hyperactivity and impaired discriminative performance of SHR. The present study therefore investigated whether there was any change in the α2-adrenoceptor mediated inhibition of dopamine release from nucleus accumbens slices of SHR in comparison with their normotensive Wistar-Kyoto (WKY) controls. The electrically stimulated release of [3H]dopamine (DA) from nucleus accumbens slices was decreased to a similar extent by UK14,304, an α2-adrenoceptor agonist, in SHR and WKY. Basal norepinephrine (NE) levels were increased in locus coeruleus (LC) and A2 noradrenergic nuclei, but ...

TY - JOUR. T1 - MTH1, an oxidized purine nucleoside triphosphatase, protects the dopamine neurons from oxidative damage in nucleic acids caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. AU - Yamaguchi, H.. AU - Kajitani, K.. AU - Dan, Y.. AU - Furuichi, M.. AU - Ohno, M.. AU - Sakumi, K.. AU - Kang, D.. AU - Nakabeppu, Yusaku. PY - 2006/4/1. Y1 - 2006/4/1. N2 - We previously reported that 8-oxoguanine (8-oxoG) accumulates in the cytoplasm of dopamine neurons in the substantia nigra of patients with Parkinsons disease and the expression of MTH1 carrying an oxidized purine nucleoside triphosphatase activity increases in these neurons, thus suggesting that oxidative damage in nucleic acids is involved in dopamine neuron loss. In the present study, we found that levels of 8-oxoG in cellular DNA and RNA increased in the mouse nigrostriatal system during the tyrosine hydroxylase (TH)-positive dopamine neuron loss induced by the administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine ...

The highly prevalent parasite Toxoplasma gondii manipulates its hosts behavior. In infected rodents, the behavioral changes increase the likelihood that the parasite will be transmitted back to its definitive cat host, an essential step in completion of the parasites life cycle. The mechanism(s) responsible for behavioral changes in the host is unknown but two lines of published evidence suggest that the parasite alters neurotransmitter signal transduction: the disruption of the parasite-induced behavioral changes with medications used to treat psychiatric disease (specifically dopamine antagonists) and identification of a tyrosine hydroxylase encoded in the parasite genome. In this study, infection of mammalian dopaminergic cells with T. gondii enhanced the levels of K+-induced release of dopamine several-fold, with a direct correlation between the number of infected cells and the quantity of dopamine released. Immunostaining brain sections of infected mice with dopamine antibody showed intense

TY - JOUR. T1 - Bilateral effects of unilateral GDNF administration on dopamine- and GABA-regulating proteins in the rat nigrostriatal system. AU - Salvatore, Michael F.. AU - Gerhardt, Greg A.. AU - Dayton, Robert D.. AU - Klein, Ronald L.. AU - Stanford, John A.. PY - 2009/9. Y1 - 2009/9. N2 - Dopamine (DA) affects GABA neuronal function in the striatum and together these neurotransmitters play a large role in locomotor function. We recently reported that unilateral striatal administration of GDNF, a growth factor that has neurotrophic effects on DA neurons and enhances DA release, bilaterally increased striatal neuron activity related to locomotion in aged rats. We hypothesized that the GDNF enhancement of DA function and resulting bilateral enhancement of striatal neuronal activity was due to prolonged bilateral changes in DA- and GABA-regulating proteins. Therefore in these studies we assessed dopamine- and GABA-regulating proteins in the striatum and substantia nigra (SN) of 24 month old ...

i] Correa M., Salamone J.D. THE MYSTERIOUS MOTIVATIONAL FUNCTIONS OF MESOLIMBIC DOPAMINE Neuron 2012 Nov 8; 76(3): 470-485. (source). [ii] Treadway T.T. et. Al. Dopaminergic Mechanisms of Individual Differences in Human Effort-Based Decision-Making The Journal of Neuroscience, 2 May 2012, 32(18):6170-6176 (source). [iii] Qi J., Zhang S., Wang H.L., Wang H., de Jesus Aceves Buendia J., Hoffman A.F., Lupica C.R., Seal R.P., Morales M. A glutamatergic reward input from the dorsal raphe to ventral tegmental area dopamine neurons. Nature Communications. 2014 Nov 12;5:5390. (source). [iv] Berridge K.C., Robinson T.E. What is the role of dopamine in reward: hedonic impact, reward learning, or incentive salience? Brain Research; Brain Research Reviews. 1998 Dec;28(3):309-69. (source). [v] Testa B., Mayer J.M. (1 August 2003). Hydrolysis in Drug and Prodrug Metabolism. John Wiley & Sons. pp. 109-. ISBN 978-3-906390-25-3. (source). [vi] Peterson A.L., Gilman T.L., Banks M.L., Sprague J.E. ...

Disrupted mesocortical dopamine contributes to cognitive symptoms of Parkinsons disease (PD). Past work has implicated medial frontal neurons expressing D1 dopamine receptors (D1DRs) in temporal processing. Here, we investigated whether these neurons can compensate for behavioral deficits resulting from midbrain dopamine dysfunction. We report three main results. First, both PD patients and mice with ventral tegmental area (VTA) dopamine depletion had attenuated delta activity (1-4 Hz) in the medial frontal cortex (MFC) during interval timing. Second, we found that optogenetically stimulating MFC D1DR neurons could increase ramping activity among MFC neurons. Finally, stimulating MFC D1DR neurons specifically at delta frequencies (2 Hz) compensated for deficits in temporal control of action caused by VTA dopamine depletion. Our results suggest that cortical networks can be targeted by frequency-specific brain stimulation to improve dopamine-dependent cognitive processing.

TY - JOUR. T1 - The Roles of Accumbal Dopamine D1 and D2 Receptors in Maternal Memory in Rats. AU - Parada, Mayte. AU - King, Samantha. AU - Li, Ming. AU - Fleming, Alison S.. N1 - Copyright: Copyright 2011 Elsevier B.V., All rights reserved.. PY - 2008/4. Y1 - 2008/4. N2 - Female rats show enhanced maternal responsiveness toward their young if they have had maternal experiences before. This kind of maternal experience-based memory is critically dependent on the mesolimbic dopamine (DA) system, especially the nucleus accumbens (NA) shell. However, the relative contributions of the two main DA receptor systems (D1 and D2) within the shell have not been delineated. This study investigates the roles of dopamine D1 and D2 receptors in maternal memory by infusing a selective D1 antagonist, SCH-23390; a selective D2 antagonist, sulpiride; or a combination D1/D2 antagonist, cis-Z-flupenthixol, into the NA shell of postpartum female rats. Sulpiride-infused rats showed a significantly longer latency to ...

Abstract: The ability of estrogen to modulate mesolimbic dopamine (DA) was examined using in vivo voltammetry. Estrogen priming (5 μg, 48 h) of ovariectomized (ovx) female rats resulted in a slight decrease in K+-stimulated DA release measured in the nucleus accumbens: this decrease was accompanied by a significant increase in both DA reuptake and DA clearance times. Following estrogen priming nomifensine, a potent inhibitor of the DA uptake carrier, was still able to potentiate K+-stimulated DA release and alter the time course of DA availability, but the response was attenuated compared with ovx controls. Direct infusion of 17β-estradiol hemisuccinate (17β-E, 20-50 pg) into the nucleus accumbens resulted in a biphasic potentiation of K+-stimulated release. An initial increase in release was observed 2 min after 17β-E infusion; this increase, although reduced by 15 min, was still significantly higher than control values. A subsequent potentiation was observed 60 min after the initial 17β-E ...

This work extends our understanding of the circuitry underlying DA-mediated opioid reward. Disinhibition of VTA DA neurons can produce positive reinforcement, and the present study shows that opioids can influence the inhibition of VTA DA neurons by the VP through two separate mechanisms: inhibition of their somata in the VP and inhibition of their GABAergic terminals on VTA DA neurons.. The apparent direct GABAergic synaptic connection of VP terminals to VTA cell bodies parallels earlier observations that globus pallidus inputs onto DA neurons of the substantia nigra often form baskets around the soma and proximal dendrites of nigral cells (Smith and Bolam, 1990). Therefore, VP inputs are positioned to strongly inhibit cell bodies and thus influence the overall firing rate of midbrain neurons. Our findings also extend our understanding of an in vivo study showing that VP GABAergic inputs control the population activity of VTA DA neurons (Floresco et al., 2003).. Similar to inputs arising from ...

Cocaine strengthens excitatory synapses onto midbrain dopamine neurons through the synaptic delivery of GluR1-containing AMPA receptors. This cocaine-evoked plasticity depends on NMDA receptor activation, but its behavioral significance in the context of addiction remains elusive. Here, we generated mice lacking the GluR1, GluR2, or NR1 receptor subunits selectively in dopamine neurons. We report that in midbrain slices of cocaine-treated mice, synaptic transmission was no longer strengthened when GluR1 or NR1 was abolished, while in the respective mice the drug still induced normal conditioned place preference and locomotor sensitization. In contrast, extinction of drug-seeking behavior was absent in mice lacking GluR1, while in the NR1 mutant mice reinstatement was abolished. In conclusion, cocaine-evoked synaptic plasticity does not mediate concurrent short-term behavioral effects of the drug but may initiate adaptive changes eventually leading to the persistence of drug-seeking ...

TY - JOUR. T1 - Protective effects of pergolide on dopamine levels in the 6-hydroxydopamine-lesioned mouse brain. AU - Asanuma, M.. AU - Ogawa, N.. AU - Nishibayashi, S.. AU - Kawai, M.. AU - Kondo, Yoichi. AU - Iwata, E.. PY - 1995/1/1. Y1 - 1995/1/1. N2 - Pergolide, along with bromocriptine and lisuride, is one of the most active dopamine receptor agonists. To determine whether or not pergolide protects against dopaminergic neuronal damage, via its activity on monoamine metabolism, we studied the effects of pergolide pretreatment on changes in monoamines and their metabolites in the mouse striatum after intracerebroventricular injection of 6-hydroxydopamine with pretreatment of desipramine. After intracerebroventricular administration of 6-hydroxydopamine (40 μg) in mice, the levels of dopamine and its metabolites (DOPAC, HVA) in the striatum rapidly decreased to 49%, 29% and 68%, respectively, of the naive controls at week 1 but then gradually recovered to control levels at weeks 2 and 4. ...

Protein interacting with C-kinase 1 (PICK1) is a widely expressed scaffold protein known to interact via its PSD-95/discs-large/ZO-1 (PDZ)-domain with several membrane proteins including the dopamine (DA) transporter (DAT), the primary target for cocaines reinforcing actions. Here, we establish the importance of PICK1 for behavioral effects observed after both acute and repeated administration of cocaine. In PICK1 knock-out (KO) mice, the acute locomotor response to a single injection of cocaine was markedly attenuated. Moreover, in support of a role for PICK1 in neuroadaptive changes induced by cocaine, we observed diminished cocaine intake in a self-administration paradigm. Reduced behavioral effects of cocaine were not associated with decreased striatal DAT distribution and most likely not caused by the ∼30% reduction in synaptosomal DA uptake observed in PICK1 KO mice. The PICK1 KO mice demonstrated preserved behavioral responses to DA receptor agonists supporting intact downstream DA ...

amphetamine, cyclic voltammetry, dopamine, dopamine transporter, GDNF, striatum, MICE LACKING GDNF, NEUROTROPHIC FACTOR, IN-VIVO, TYROSINE-HYDROXYLASE, SUBSTANTIA-NIGRA, ALPHA-SYNUCLEIN, NERVOUS-SYSTEM, RAT, RELEASE, ...

Parkinsons disease (PD), a condition characterized by muscle stiffness and uncontrollable shaking, is caused by the progressive degeneration of midbrain neurons that control motor function. These neurons produce the neurotransmitter dopamine (DA), which has long been associated with motor function. As the neurons deteriorate, dopamine levels plummet, eventually leading to the symptoms of this debilitating disease. To understand the pathological processes leading to PD, researchers have developed rodent models that either recapitulate the loss of DA or recapitulate the neurodegenerative process. But many of these models only achieve incomplete DA depletion, often precluding an accurate recapitulation of the neurological manifestations of PD. Now, Tatyana Sotnikova and colleagues have successfully induced a reliable but transient recapitulation of PD symptoms in mice.. Normally, neurons have a large intracellular storage pool of DA. After its release, DA is rapidly recycled back into neurons ...

d-Amphetamine is markedly more potent an inhibitor of catecholamine uptake by norepinephrine neurons in the brain than is 1-amphetamine, whereas the two isomers are equally active in inhibiting catecholamine uptake by the dopamine neurons of the corpus striatum. In behavioral studies, d-amphetamine is ten times as potent as 1-amphetamine in enhancing locomotor activity, while it is only twice as potent in eliciting a compulsive gnawing syndrome. This suggests that the locomotor stimulation induced by amphetamine involves central norepinephrine, while dopamine neurons play an important role in the induced compulsive gnawing behavior. Assessment of differential actions of d- and 1-amphetamine may be an efficient method to differentiate behaviors involving norepinephrine or dopamine in the brain. ...

The data presented here demonstrate that MAM-treated rats display a pathologically enhanced DA neuron drive in the form of an increase in DA neuron population activity. Moreover, this seems to be associated with an increase in the spontaneous firing rate of vHipp neurons unrelated to changes in patterned activity at the single cell level. Furthermore, we suggest that the aberrant DA neuron activity is attributed to the increased vHipp activity because intra-vHipp TTX administration normalizes both the augmented DA neuron activity and the behavioral hyper-responsivity to amphetamine. It is important to note that TTX administration did not eliminate the response to amphetamine, but instead restored it to the level found in controls.. An association between hippocampal activity and ascending DA function has been suggested previously (Legault and Wise, 1999; Floresco et al., 2001, 2003; Lodge and Grace, 2006a). Thus, the vHipp can modulate DA neuron population activity via a multisynaptic ...

STUDY OBJECTIVE: To investigate the early blood pressure effects of vasopressin compared with titrated catecholamines as initial drug therapy in patients with septic shock.. DESIGN: Retrospective cohort, single-center study.. SETTING: Intensive care units at the Mayo Clinic, Rochester, Minnesota.. PATIENTS: Fifty, 49, and 51 intensive care patients treated initially with vasopressin, norepinephrine, and dopamine, respectively.. INTERVENTION: Patients received either intravenous infusion of fixed-dose vasopressin 0.04 U/minute or titrated infusions of norepinephrine or dopamine for low systemic arterial pressures.. MEASUREMENTS AND MAIN RESULTS: Patients treated with vasopressin, norepinephrine, and dopamine were similar in all measured characteristics except for their score on the Acute Physiology and Chronic Health Evaluation (APACHE) III (dopamine , vasopressin, p=0.049), renal comorbidities (dopamine , vasopressin, p=0.03) and baseline mean arterial pressure (MAP) (norepinephrine , ...

AGE and Parkinson s Disease Parkinson s disease (PD), the second most common neurodegenerative disorder in the United States, is characterized by a loss of voluntary movement as a result of the death of neurons in an area of the midbrain known as the substantia nigra. The neurons in that area of the brain contain the neurotransmitter dopamine. In Parkinson s disease, dopamine-transmitting neurons in this area die by apoptosis, triggered by free radicals, that are generated in dopamine metabolism. Recent evidence indicates that the substantia nigra of patients with PD contains increased iron,which enhances oxidation, and decreased glutathione, which protects against the formation of free radicals. Further, the end products of peroxidized lipids are increased in the substantia nigra of patients with PD, supporting the notion that free radicals contribute to dopamine neuronal death. Thus antioxidant therapies may slow the rate of progression of PD. Aged garlic extract, with its high antioxidant ...

AGE and Parkinson s Disease Parkinson s disease (PD), the second most common neurodegenerative disorder in the United States, is characterized by a loss of voluntary movement as a result of the death of neurons in an area of the midbrain known as the substantia nigra. The neurons in that area of the brain contain the neurotransmitter dopamine. In Parkinson s disease, dopamine-transmitting neurons in this area die by apoptosis, triggered by free radicals, that are generated in dopamine metabolism. Recent evidence indicates that the substantia nigra of patients with PD contains increased iron,which enhances oxidation, and decreased glutathione, which protects against the formation of free radicals. Further, the end products of peroxidized lipids are increased in the substantia nigra of patients with PD, supporting the notion that free radicals contribute to dopamine neuronal death. Thus antioxidant therapies may slow the rate of progression of PD. Aged garlic extract, with its high antioxidant ...

TY - JOUR. T1 - Dopamine inhibition of tryptophan hydroxylase in molluscan nervous tissue homogenates. T2 - Evidence for intracellular site of action. AU - Hiripi, Laszlo. AU - Stefano, George B.. PY - 1980/1/1. Y1 - 1980/1/1. N2 - PCPA, dopamine and the dopamine agonist epinine inhibited trytophan hydroxylase activity in nervous tissue homogenates of Anodonta cygnea and Mytilus edulis (Bivalvia). Haloperidol did not affect tryptophan hydroxylase activity in the homogenates nor did it antagonize dopamine action.. AB - PCPA, dopamine and the dopamine agonist epinine inhibited trytophan hydroxylase activity in nervous tissue homogenates of Anodonta cygnea and Mytilus edulis (Bivalvia). Haloperidol did not affect tryptophan hydroxylase activity in the homogenates nor did it antagonize dopamine action.. UR - http://www.scopus.com/inward/record.url?scp=0019186605&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0019186605&partnerID=8YFLogxK. U2 - ...

Abstract : Lesch-Nyhan disease is a neurogenetic disorder caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit a characteristic pattern of neurological and behavioral features attributable in part to dysfunction of basal ganglia dopamine systems. In the current studies, striatal dopamine loss was investigated in five different HPRT-deficient strains of mice carrying one of two different HPRT gene mutations. Caudoputamen dopamine concentrations were significantly reduced in all five of the strains, with deficits ranging from 50.7 to 61.1%. Mesolimbic dopamine was significantly reduced in only three of the five strains, with a range of 31.6-38.6%. The reduction of caudoputamen dopamine was age dependent, emerging between 4 and 12 weeks of age. Tyrosine hydroxylase and aromatic amino acid decarboxylase, two enzymes responsible for the synthesis of dopamine, were reduced by 22.4-37.3 and 22.2-43.1%, respectively. These ...

MESSRIPOUR, Manoochehr y MESRIPOUR, Azadeh. Age related interaction of dopamine and serotonin synthesis in striatal synaptosomes. Biocell [online]. 2013, vol.37, n.2, pp.17-21. ISSN 0327-9545.. Tyrosine hydroxylase and tryptophan hydroxylase are key rate limiting enzymes in the biosyn-thesis of dopamine and serotonin, respectively. Since both enzymes are active in striatum, and affected by age, this study was undertaken to investigate interaction between dopamine and serotonin synthesis in brain striatal synaptosomes of aging rat. Male Wistar rats (3 and 30 month old) were killed by decapitation and brain striatal synaptosomes were prepared by discontinuous Ficoll/sucrose gradient technique. Synaptosomes were incubated in the presence of added pargiline (monoamineoxidase inhibitor), dopamine or serotonin synthesized during 25 min was measured by HPLC, employing electrochemical detection. Dopamine synthesis in synaptosomes prepared from young animals was markedly inhibited by addition of 5 μM ...

TY - JOUR. T1 - Correlation between body mass index and striatal dopamine transporter availability in healthy volunteers-A SPECT study. AU - Chen, Po See. AU - Yang, Yen Kuang. AU - Yeh, Tzung Lieh. AU - Lee, I. Hui. AU - Yao, Wei Jen. AU - Chiu, Nan Tsing. AU - Lu, Ru Band. PY - 2008/3/1. Y1 - 2008/3/1. N2 - Recent lines of research suggest that, in addition to hypothalamic sites, the striatum dopaminergic system may be a target for regulating homeostasis that may be represented by the body mass index (BMI). Although it has been reported that the striatal dopamine receptor (DRD2) availability of very obese individuals was reduced in proportion to their BMI, the correlation between the striatal dopamine system and the BMI in healthy individuals remains unclear. To investigate this relationship, the striatal dopamine transporter (DAT) availability of 50 healthy volunteers was measured using single position emission computational topography (SPECT) and [99mTc]-TRODAT-1. The serum levels of sugar, ...

Catechol-O-methyltransferase (COMT) catabolises the catecholamine neurotransmitters and influences cognitive function. COMT modulates dopamine levels in the prefrontal cortex and its action in this region is generally invoked to explain its effects on cognition. However, its role in other brain regions important for cognitive function remains largely unexplored. Here, we investigated COMTs impact on dopamine metabolism in the hippocampus and hippocampal-dependent behaviour. We examined the acute effects of a centrally-acting COMT inhibitor, tolcapone (30 mg/kg i.p.), on dopamine metabolism in the rat dorsal hippocampus, assessed both in tissue homogenates and extracellularly, using in vivo microdialysis. Additionally, we investigated the effect of tolcapone on delayed-rewarded alternation and spatial novelty preference, behavioural tasks which are dependent on the dorsal hippocampus. Tolcapone significantly modulated dopamine metabolism in the dorsal hippocampus, as indexed by the depletion of

TY - JOUR. T1 - Caspase-dependent and -independent cell death pathways in primary cultures of mesencephalic dopaminergic neurons after neurotoxin treatment. AU - Han, Baek S.. AU - Hong, Hyun Seung. AU - Choi, Won Seok. AU - Markelonis, George J.. AU - Oh, Tae H.. AU - Oh, Young Jun. PY - 2003/6/15. Y1 - 2003/6/15. N2 - Although the cause of neuronal death in Parkinsons disease (PD) is mainly unknown, growing evidence suggests that both apoptotic and non-apoptotic death may occur in PD. Using primary cultures of mesencephalic dopaminergic neurons and the MN9D dopaminergic neuronal cell line, we attempted to evaluate specifically the existence of the mitochondrial apoptotic pathway, focusing on the mitochondrial release of cytochrome c to the activation of the caspases after 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenylpyridinium (MPP+) treatment. Both immunofluorescent labeling and immunoblot analysis indicated mitochondrial release of cytochrome c into the cytosol after 6-OHDA or MPP+ ...

Uridine (15mg/kg/day, i.p.), haloperidol (1mg/kg/day, i.p.), uridine (15mg/kg/day, i.p.) plus haloperidol (1mg/kg/day, i.p.) or saline have been chronically administered to Sprague-Dawley male rats. Following 1 week of wash-out, the effects of these treatments on basal striatal dopamine (DA) release as well as on the DA release induced by an acute haloperidol challenge (2mg/kg, i.p.) were studied by means of intracerebral microdialysis. Behavioural tests such as haloperidol-induced catalepsy or apomorphine-induced stereotypics were also performed 4-7 days after drug withdrawal. The chronic treatment with uridine alone or associated with haloperidol markedly reduced DA release induced by an acute haloperidol challenge. The behavioural studies also indicated a change in DA-related behaviours in these conditions. The animals chronically treated with uridine showed significant increases in the stereotypy scores and in the catalepsy induced by an acute haloperidol challenge with respect to saline ...

TY - JOUR. T1 - Insulin-like peptide DILP6 regulates juvenile hormone and dopamine metabolism in Drosophila females. AU - Rauschenbach, I. Yu.. AU - Karpova, E. K.. AU - Burdina, E. V.. AU - Adonyeva, N. V.. AU - Bykov, R. A.. AU - Ilinsky, Y. Y.. AU - Menshanov, P. N.. AU - Gruntenko, N. E.. N1 - Copyright © 2016 Elsevier Inc. All rights reserved.. PY - 2017/3/1. Y1 - 2017/3/1. N2 - Insulin-like peptide DILP6 is a component of the insulin/insulin-like growth factor signalling pathway of Drosophila. Juvenile hormone (JH) and dopamine (DA) are involved in the stress response and in the control of reproduction. In this study, we investigate whether DILP6 regulates the JH and DA levels by studying the effect of a strong hypomorphic mutation dilp6(41) on JH and DA metabolism in D. melanogaster females. We show that DILP6 regulates JH and DA metabolism: the mutation dilp641 results in a reduction in JH-hydrolysing activity and an increase in the activities of DA synthesis enzymes (alkaline ...

The dopamine receptor D4 is a G protein-coupled receptor encoded by the DRD4 gene on chromosome 11 at 11p15.5. The structure of DRD4 was recently reported in complex with the antipsychotic drug nemonapride. As with other dopamine receptor subtypes, the D4 receptor is activated by the neurotransmitter dopamine. It is linked to many neurological and psychiatric conditions including schizophrenia and bipolar disorder, ADHD, addictive behaviors, Parkinsons disease, and eating disorders such as anorexia nervosa. It is also a target for drugs which treat schizophrenia and Parkinson disease. The D4 receptor is considered to be D2-like in which the activated receptor inhibits the enzyme adenylate cyclase, thereby reducing the intracellular concentration of the second messenger cyclic AMP. The human protein is coded by the DRD4 on chromosome 11 located in 11p15.5.[citation needed] There are slight variations (mutations/polymorphisms) in the human gene: A 48-base pair VNTR in exon 3 C-521T in the ...

Sexual chemosignals detected by vomeronasal and olfactory systems mediate intersexual attraction in rodents, and act as a natural reinforcer to them. The mesolimbic pathway processes natural rewards, and the nucleus accumbens receives olfactory information via glutamatergic projections from the amygdala. Thus, the aim of this study was to investigate the involvement of the mesolimbic pathway in the attraction towards sexual chemosignals. Our data show that female rats with no previous experience with males or their chemosignals display an innate preference for male-soiled bedding. Focal administration of the opioid antagonist β-funaltrexamine into the posterior ventral tegmental area does not affect preference for male chemosignals. Nevertheless, exposure to male-soiled bedding elicits an increase in dopamine efflux in the nucleus accumbens shell and core, measured by microdialysis. Infusion of the opioid antagonist naltrexone in the accumbens core does not significantly affect dopamine efflux during

Amphetamine and methylphenidate are not (direct) dopamine agonists.. Dopamine agonists are the substances that would specifically bind to dopamine receptors and activate them, thereby mimicking the effects of dopamine release.. Amphetamine/methylphenidate are so-called indirect sympatomimetics. This means that they stimulate the simpatyc nervous systems (with neurotransmitters noradrenaline and dopamine in CNS), but in indirect way: they dont bind to the receptors. Rather, they promote the massive neurotransmitter release from the presynaptic part. The released transmitter (DA, NA) then just diffuses to the postsynaptic membrane and binds to its own receptors.. There are some works done on investigating the effect of these substances on parasympatic system with acetylcholine as neurotransmitter.. Sympatomimetics like amphetamine generally lead to increase of acetylcholine release throurout the nervous system: in hippocampus and caudate nucleus, nucleus accumbens and generally in forebrain and ...

Chen, Y, Phillips, KG and Sher, E (2003) Subtypes of excitatory cholinergic receptors on dopaminergic cells in the rat ventral tegmental area In: 3rd Congress of the Federation-of-European-Physiological-Societies, 2003-06-28 - 2003-07-02, NICE, FRANCE. Full text not available from this repository ...

Background and Objective: Parkinsons disease (PD) is the second most common neurodegenerative disease after Alzheimers disease that affects 3% of the population. PD involves a progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc) and subsequent loss of dopamine. Dopamine depletion leads to movement dysfunction and is accompanied with tremor, rigid muscles and impaired balance. Mechanisms of the pathogenesis of PD include oxidative stress and inflammation. Cinnamaldehyde acts as a powerful antioxidant and anti-inflammatory agent. This research is focused on the effects of cinnamaldehyde on neurons of SNc of mouse model of PD. Materials and Methods: Adult male mice with an average weight of 25-35 g were divided into 4 groups of 5 each: group 1: control PBS, group2: MPTP, group 3: MPTP + cinnamaldehyde pretreatment (30 mg/kg), and group 4: MPTP + cinnamaldehyde treatment (30 mg/kg). Rotarod test was used to assess motor and balance of the mice. After behavioral

In this article, the authors report that the temporal precision of the reward prediction error signal encoded by midbrain dopamine neurons declines as the delay between a reward predicting stimulus and an expected reward increases. The temporal precision of the neural signal is qualitatively similar to that of anticipatory behavior. Midbrain dopamine neurons are activated when reward is greater than predicted, and this error signal could teach target neurons both the value of reward and when it will occur. We used the dopamine error signal to measure how the expectation of reward was distributed over time. Animals were trained with fixed-duration intervals of 1-16 s between conditioned stimulus onset and reward. In contrast to the weak responses that have been observed after short intervals (1-2 s), activations to reward increased steeply and linearly with the logarithm of the interval. Results with varied stimulus-reward intervals suggest that the neural expectation was substantial after just half an

Exogenous Dopamine is unable to cross the tight junctions of the endothelial cells in the blood-brain barrier (BBB). Dopamine has no clinically significant endogenous transporter on the blood-brain barrier and is otherwise too polar of a molecule to move through the lipid membrane. Levodopa, however, utilizes a receptor on the BBB known as Large amino acid transporter (LAT) which allows it to be transported across the blood-brain barrier and decarboxylated into Dopamine. ...

A major consequence of Parkinsons disease (PD) involves the loss of dopaminergic neurons in the substantia nigra (SN) and a subsequent loss of dopamine (DA) in the striatum. We have shown that glial cell line-derived neurotrophic factor (GDNF) shows robust restorative and protective effects for DA neurons in rats, non-human primates and possibly in humans. Despite GDNFs therapeutic potential, its clinical value has been questioned due to its limited diffusion to target areas from its large size and chemical structure. Several comparatively smaller peptides are thought to be generated from the prosequence. A five amino-acid peptide, dopamine neuron stimulating peptide-5 (DNSP-5), has been proposed to demonstrate biological activity relevant to neurodegenerative disease. We tested the in vitro effects of DNSP-5 in primary dopaminergic neurons dissected from the ventral mesencephalon of E14 Sprague Dawley rat fetuses. Cells were treated with several doses (0.03, 0.1, 1.0, 10.0 ng/mL) of GDNF, ...

Dopamine (DA) neurotransmission in the nucleus accumbens (NAc) is critically involved in normal as well as maladaptive motivated behaviors including drug addiction. Whether the striatal neuromodulator nitric oxide (NO) influences DA release in NAc is unknown. We investigated whether exogenous NO modulates DA transmission in NAc core and how this interaction varies depending on the frequency of presynaptic activation. We detected DA with cyclic voltammetry at carbon-fiber microelectrodes in mouse NAc in slices following stimuli spanning a full range of DA neuron firing frequencies (1-100 Hz). NO donors 3-morpholinosydnonimine hydrochloride (SIN-1) or z-1-[N-(3-ammoniopropyl)-N-(n-propyl)amino]diazen-1-ium-1,2-diolate (PAPA/NONOate) enhanced DA release with increasing stimulus frequency. This NO-mediated enhancement of frequency sensitivity of DA release was not prevented by inhibition of soluble guanylyl cyclase (sGC), DA transporters, or large conductance Ca(2+)-activated K(+) channels, and did not

The nigrostriatal pathway, or the nigrostriatal bundle (NSB), is a dopaminergic pathway that connects the substantia nigra with the striatum. It is one of the four major dopamine pathways in the brain, and is particularly involved in the production of movement, as part of a system called the basal ganglia motor loop. Dopamine releasing neurons of this pathway release several other neurotransmitters, including glutamate and GABA.[1][2] Loss of dopamine neurons in the substantia nigra is one of the main pathological features of Parkinsons disease,[3] leading to a marked reduction in dopamine function in this pathway. The symptoms of the disease typically do not show themselves until 80-90% of dopamine function has been lost. This pathway is also implicated in producing tardive dyskinesia, one of the side-effects of antipsychotic drugs. These medications (in particular the older typical antipsychotics) block D2 dopamine receptors in multiple pathways in the brain. The desired clinical effect of ...

Dopamine regulates reproduction in part by modulating neuronal activity within the hypothalamic-pituitary-gonadal (HPG) axis. Previous studies suggested numerous mechanisms by which dopamine exerts inhibitory control over the HPG axis, ultimately changing the levels of sex steroids that regulate reproductive behaviors. However, it is not known whether these mechanisms are conserved across vertebrate species. In particular, it is unknown whether mechanisms underlying dopaminergic control of reproduction are shared between mammals and teleost fish. In mammals, dopamine directly inhibits GnRH1 hypothalamic neurons, the gatekeepers for activation of the HPG axis. Here, we demonstrate, for the first time in teleost fish, dopaminergic control of GnRH1 neurons via direct dopamine receptor type-2 (D2R) mediated inhibition within the hypothalamus. These results suggest that direct dopaminergic control of GnRH1 neurons via interactions in the hypothalamus is not exclusive to tetrapod reproductive control, ...

TY - JOUR. T1 - Noradrenergic and dopaminergic projections to the medial preoptic area of the rat. A combined horseradish peroxidase/catecholamine fluorescence study. AU - Day, Trevor A.. AU - Blessing, William. AU - Willoughby, John O.. PY - 1980. Y1 - 1980. KW - catecholamine. KW - dopaminergic projection. KW - HRP. KW - hypothalamus. KW - noradrenergic projection. UR - http://www.scopus.com/inward/record.url?scp=0018876246&partnerID=8YFLogxK. U2 - 10.1016/0006-8993(80)90185-7. DO - 10.1016/0006-8993(80)90185-7. M3 - Article. C2 - 7388608. AN - SCOPUS:0018876246. VL - 193. SP - 543. EP - 548. JO - Brain Research. JF - Brain Research. SN - 0006-8993. IS - 2. ER - ...

Stop smoking, through stimulating specific points in the ear causing the brain to release neurotransmitters (such as endorphins and dopamine) that help to break the addiction cycle. Theralase combines treatment with behavioural modification addiction counseling and nutritional guidance to create programs with a very high rate of success.. Using the principals of ear acupuncture (auriculotherapy), targets specific ear points to induce the brain chemistry to release neurotransmitters such as dopamine, serotonin and endorphins (the pleasure chemicals of the brain) to travel to different sections of the brain, which help to break the addiction cycle. The nucleus accumbens mediates the release of the neurotransmitter dopamine, which underlies pleasure and relaxation. But the dopamine itself is released from the ventral tegmental area (VTA), another contender for the title of pleasure center. The VTA releases dopamine to the nucleus accumbens, the prefrontal cortex, amygdala, and septum, all of ...

Cocaine addiction, a serious public health concern associated with significant medical, social, and economic consequences, is difficult to treat using traditional psychosocial and behavioral therapies. Despite testing of a number of different agents for cocaine dependency, there remains no proven pharmacologic treatment for cocaine addiction.. The addictive properties of cocaine have been associated with its actions on mesotelencephalic dopamine reward pathways in the central nervous system (CNS). Cocaine administration increases the levels of dopamine, a neurotransmitter associated with sensations of pleasure and reward. Therefore, blocking cocaine-induced increases in dopamine levels represents a valid pharmaceutical approach to the treatment of cocaine addiction.. Another neurotransmitter, gamma-aminobutyric acid (GABA), suppresses striatal dopamine release, and attenuates cocaine-induced increases in extracellular and synaptic dopamine levels in the striatum and nucleus accumbens in animal ...

Title: Parallel Roles for Dopamine in Pathological Gambling and Psychostimulant Addiction. VOLUME: 2 ISSUE: 1. Author(s):Martin Zack and Constantine X. Poulos. Affiliation:Clinical Neuroscience Section, Centre for Addiction and Mental Health (CAMH), 33 Russell Street, Toronto, Ontario, M5S 2S1, Canada.. Keywords:Pathological gambling, psychostimulant, dopamine, addiction, sensitization. Abstract: A variety of evidence suggests important commonalities in the neurochemical basis of reinforcement in pathological gambling (PG) and psychostimulant addiction. This article focuses on the parallel and specific roles that dopamine (DA) activation plays in these two disorders, beyond its generic role in reinforcement. A psychostimulant-mimetic model for PG is proposed based on evidence from the following domains: Acute subjective-behavioral effects of gambling and psychostimulants; Effects of anticipated rewards and uncertainty of reward delivery (key elements of gambling) on DA release; Relationship ...

phdthesis{82d6999a-c9af-4e9a-a5bd-5475ffcf7ede, abstract = {This study has investigated the impact of presynaptic factors on the development of dyskinesia during chronic L-DOPA treatment in a rat model of Parkinsons disease (PD). The mechanisms causing dyskinesia are not completely understood but have been proposed to involve changes in gene and protein expression in striatal neurons, which are the main target of dopamine (DA) projections from the substantia nigra pars compacta (SNpc). It has recently become evident that also factors presynaptic of the striatal neurons can contribute to the pathophysiology of dyskinesia. Indeed, abnormally large increases in extracellular DA concentrations have recently been documented in both animal models of PD and human patients following treatment with L-DOPA. The mechanisms underlying such increases have not been resolved. This thesis work has addressed two factors that may determine large surges of extracellular DA upon treatment with L-DOPA, namely ...

Parkinsons disease (PD) is characterised by dopaminergic cell loss within the substantia nigra pars compacta (SNc) that leads to reduced striatal dopamine content and resulting motor deficits. Identifying new strategies to protect these cells from degeneration and retain striatal dopaminergic innervation is therefore of great importance. Chondroitin sulphate proteoglycans (CSPGs) are recognised contributors to the inhibitory extracellular milieu known to hinder tissue recovery following CNS damage. Digestion of these molecules by the bacterial lyase chondroitinase ABC (ChABC) has been shown to promote functional recovery in animal models of neurological injury. Although ChABC has been shown to promote sprouting of dopaminergic axons following transection of the nigrostriatal pathway, its ability to protect against nigrostriatal degeneration in a toxin-based module with better construct validity for PD has yet to be explored. Here we examined the neuroprotective efficacy of ChABC treatment in the full

Parkinsons disease is a movement disorder characterized by degeneration of dopaminergic neurons in the substantia nigra pars compacta. Dopaminergic neuronal loss also occurs in Drosophila melanogaster upon directed expression of α-synuclein, a protein implicated in the pathogenesis of Parkinsons disease and a major component of proteinaceous Lewy bodies. We report that directed expression of the molecular chaperone Hsp70 prevented dopaminergic neuronal loss associated with α-synuclein in Drosophilaand that interference with endogenous chaperone activity accelerated α-synuclein toxicity. Furthermore, Lewy bodies in human postmortem tissue immunostained for molecular chaperones, also suggesting that chaperones may play a role in Parkinsons disease progression. ...

TY - JOUR. T1 - Either isoform of the dopamine D2 receptor can mediate dopaminergic repression of the rat prolactin promoter. AU - McChesney, Ruth. AU - Sealfon, Stuart C.. AU - Tsutsumi, Manami. AU - Dong, Ke Wen. AU - Roberts, James L.. AU - Bancroft, Carter. PY - 1991/8. Y1 - 1991/8. N2 - Hypophyseal portal dopamine is a major negative regulator of pituitary prolactin (PRL) production. Dopamine has been reported to repress PRL gene transcription in pituitary cells. To facilitate further study of the effect of dopamine on PRL gene activation, we introduced PRL promoter and D2 receptor (D2R) constructs into GH3 cells. Since two D2R isoforms (termed D2S and D2L) have been cloned previously, we first determined which isoform(s) is present in the lactotroph by measuring the level of each mRNA species in rat prolactinoma. mRNA for each D2R isoform was found to be present, with the D2L mRNA in great (c. 6-fold) excess. Because the lactotroph contains both isoforms, the effect of each on the PRL ...

Human dopamine D3 receptor is a protein that is encoded by the dopamine receptor gene (DRD3).[2] The DRD3 gene codes for the D3 dopamine receptor that inhibits adenylyl cyclase through inhibitory G-proteins. G-protein coupled receptors are a family of transmembrane proteins that transmit chemical signals from outside the cell to cause changes inside of the cell. Adenylate cyclase is part of the G-protein receptors signaling and catalyze the conversion of ATP to cyclic AMP (cAMP).[3] The D3 receptor is located in the brain, suggesting that it plays a role in cognitive and emotional functions.[4] The human dopamine D3 receptor is membrane-bound and scattered in the cytoplasm. Receptor stimulation causes internalization of the receptors at the perinuclear areas. This is followed by the spreading of the receptors to the membrane. DRD3 is also contained in lipid rafts of renal proximal tubule cells.[5] ...

The substantia nigra pars reticulata (SNr) plays a key role in basal ganglia function. Projections from multiple basal ganglia nuclei converge at the SNr to regulate nigrothalamic output. The SNr is also characterized by abundant aminergic input, including dopaminergic dendrites and axons containing 5-hydroxytryptamine (5-HT) or histamine (HA). The functions of HA in the SNr include motor control via HA H3 receptors (H3Rs), although the mechanism remains far from elucidated. In Parkinsons disease, there is an increase in H3Rs and the density of HA-immunoreactive axons in the SN. We explored the role of H3Rs in the regulation of 5-HT release in SNr using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in rat midbrain slices. Immunohistochemistry identified a similar distribution for histaminergic and serotonergic processes in the SNr: immunoreactive varicosities were observed in the vicinity of dopaminergic dendrites. Electrically evoked 5-HT release was dependent on extracellular Ca2+ and

TY - JOUR. T1 - c-Fos induction in mesotelencephalic dopamine pathway projection targets and dorsal striatum following oral intake of sugars and fats in rats. AU - Dela Cruz, J. A. D.. AU - Coke, T.. AU - Karagiorgis, T.. AU - Sampson, C.. AU - Icaza-Cukali, D.. AU - Kest, K.. AU - Ranaldi, R.. AU - Bodnar, R. J.. PY - 2015/2. Y1 - 2015/2. KW - Ventral tegmental area. KW - Basolateral amygdala. KW - Central-cortico-medial amygdala. KW - Prelimbic medial prefrontal cortex. KW - Infralimbic medial prefrontal cortex. KW - Nucleus accumbens core. KW - Nucleus accumbens shell. KW - Dorsal striatum. U2 - 10.1016/j.brainresbull.2014.11.002. DO - 10.1016/j.brainresbull.2014.11.002. M3 - Article. C2 - 25460109. VL - 111. SP - 9. EP - 19. JO - Brain Research Bulletin. JF - Brain Research Bulletin. SN - 0361-9230. ER - ...

Parkinsons disease (PD) is characterized by a progressive degeneration of substantia nigra dopaminergic neurons projecting to the striatum. Restoration of dopamine transmission by L-DOPA relieves symptoms of PD but causes prominent side effects. There is a strong serotonin innervation of the striatum by serotonergic neurons that remains relatively preserved in PD. The study of this innervation has been largely neglected. Here, we demonstrate that chronic L-DOPA administration to 6-OHDA-lesioned rodents increases, via D1 receptors, the levels of the 5-HT1B receptor and its adaptor protein, p11, in dopamine-denervated striatonigral neurons. Using unilaterally 6-OHDA-lesioned p11 WT and KO mice, it was found that administration of a selective 5-HT1B receptor agonist, CP94253, inhibited L-DOPA-induced rotational behavior and abnormal involuntary movements in a p11-dependent manner. These data reveal an L-DOPA-induced negative-feedback mechanism, whereby the serotonin system may influence the ...

Fiorillo, Christopher D., The synaptic regulation of ventral midbrain dopamine neurons and its modulation by repeated cocaine treatment (1999). Scholar Archive. 3373 ...

Dopamine is a natural catecholamine formed by the decarboxylation of 3,4- dihydroxyphenylalanine (DOPA). It is a precursor to norepinephrine in noradrenergic nerves and is also a neurotransmitter in certain areas of the central nervous system, especially in the nigrostriatal tract, and in a few peripheral sympathetic nerves.. Dopamine produces positive chronotropic and inotropic effects on the myocardium, resulting in increased heart rate and cardiac contractility. This is accomplished directly by exerting an agonist action on beta-adrenoceptors and indirectly by causing release of norepinephrine from storage sites in sympathetic nerve endings.. Dopamines onset of action occurs within five minutes of intravenous administration, and with dopamines plasma half-life of about two minutes, the duration of action is less than ten minutes. However, if monoamine oxidase (MAO) inhibitors are present, the duration may increase to one hour. The drug is widely distributed in the body but does not cross ...

What makes Parkinsons disease distinctive from other movement disorders is that cell loss occurs in a very specific region of the brain called the substantia nigra (sub-STAN-she-uh NYE-gruh). The nerve cells, or neurons, in this region actually appear dark under a microscope (substantia nigra is Latin for black substance).. Those dark neurons produce a specific type of neurotransmitter (a chemical messenger that allows neurons to communicate) called dopamine. The neurotransmitter dopamine helps to regulate movement. This loss of dopamine is the reason that many treatments for Parkinsons Disease are intended to increase dopamine levels in the brain. ...

Mind dopamine is critically involved with movement control, and its own deficiency may be the primary reason behind engine symptoms in Parkinson disease. result from brainstem DA neurons situated in the substantia nigra pars compacta (SNc) as well as the ventral tegmental region (VTA). SNc neurons task mainly towards the caudate/putamen or dorsal striatum (nigrostriatal program), whereas VTA neurons send out their axons towards the ventral striatum like the nucleus accumbens, aswell as certain additional limbic (mesolimbic program) and cortical areas (mesocortical program). Little DA-containing cell organizations located mainly in the hypothalamus comprise the Amonafide (AS1413) tuberoinfundibular DA program [4C6]. DA is definitely synthesized from tyrosine from the rate-limiting enzyme tyrosine hydroxylase (TH), to create L-DOPA which is definitely quickly decarboxylated by = 7 per group). Striatal degrees of DA had been considerably reduced DAT-KO versus WT mice ( 0.05, Students = 5C8 per ...

The dopaminergic system has a pivotal role in the central nervous system but also plays important roles in the periphery, mainly in the endocrine system. Dopamine exerts its functions via five different receptors, named D(1)-D(5), belonging to the category of G protein coupled membrane receptors. Dopamine receptors are heterogeneously expressed in different cells, tissues and organs, where they stimulate or inhibit different functions, including neurotransmission and hormone synthesis and secretion. In particular, the dopamineric system has a pivotal role in the physiological regulation of the hypothalamus-pituitary-adrenal axis. Recent data have demonstrated the expression and function of dopamine receptors not only in endocrine organs but also in endocrine tumors, mainly those belonging to the hypothalamus-pituitary-adrenal axis, and also in the so-called neuroendocrine tumors. These data confirm the important role of the dopaminergic system in this endocrine axis, as well as in the ...

TY - JOUR. T1 - Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons. AU - Centonze, Diego. AU - Grande, Cristina. AU - Usiello, Alessandro. AU - Gubellini, Paolo. AU - Erbs, Eric. AU - Martín, Ana B.. AU - Pisani, Antonio. AU - Tognazzi, Nadia. AU - Bernardi, Giorgio. AU - Moratalla, Rosario. AU - Borrelli, Emiliana. AU - Calabresi, Paolo. PY - 2003/7/16. Y1 - 2003/7/16. N2 - By stimulating distinct receptor subtypes, dopamine (DA) exerts presynaptic and postsynaptic actions on both large aspiny (LA) cholinergic and fast-spiking (FS) parvalbumin-positive interneurons of the striatum. Lack of receptor- and isoform-specific pharmacological agents, however, has hampered the progress toward a detailed identification of the specific DA receptors involved in these actions. To overcome this issue, in the present study we used four different mutant mice in which the expression of specific DA receptors was ablated. In D1 receptor null mice, DIR-/-, ...

Researchers are not certain what causes video game addiction; however, some experts believe that elevated dopamine levels contribute heavily to the problem. The neurotransmitter dopamine works in the brains reward center. It is released during activities most people find pleasurable, including eating and consuming certain drugs. Therapists view all addictions as functioning essentially the same way. In the case of non-substance addictions, such as those to sex, gambling and gaming, the behavior takes the place of a substance. The action of playing generates a feeling of pleasure, which ensures the addict will repeat the action as often as possible. In a report published by CBC News in April 2013, a gaming addiction expert said those with certain personality disorders or disabilities are at greater risk than others. She noted that people who suffer from attention deficit hyperactivity disorder and Aspergers are particularly susceptible to gaming addiction. Those who study video game addiction ...

VEPs were recorded with three different spatial frequencies of stimulation in patients affected by idiopathic Parkinsonism and by Parkinsonian syndromes. The detection of VEP abnormalities in Parkinsons disease was dependent on the spatial frequency of the visual stimulus (a vertical square wave grating). The VEP latency was normal in Parkinsonian syndrome patients (except in one patient affected by familial Parkinsonism). Dopamine precursor therapy differently reduced the VEP latency, depending on the spatial frequency of the visual stimulus. These findings suggest that the dopaminergic mechanism involved in the generation of VEP delays is sensitive to stimulus spatial frequency. The study of VEPs before and after the administration of haloperidol confirmed this hypothesis. VEP latency did not correlate with the major clinical symptoms of Parkinsons disease and could not predict the results of chronic dopaminergic therapy.. ...

1. The renal vascular response to intravenously administered dopamine was assessed in normal man by selective renal arteriography and xenon washout. Infusion of 3 μg min−1 kg−1 induced renal vasodilatation with an increase in the cortical component of blood flow. Arterial blood pressure was not influenced and a systemic effect was not demonstrable. Lower doses did not induce a renal response. Increasing dosage raised arterial blood pressure and induced subjective symptoms, but did not result in a further increase in renal blood flow.. 2. Renal vascular resistance increased with increasing age in the normal subjects. A significant inverse relationship was found between the initial vascular resistance and the renal vasodilator response to dopamine. It thus appears that the vascular effects of increasing age (nephrosclerosis) may limit the dilator response to dopamine.. 3. It is concluded that dopamine is an effective renal cortical vasodilator when administered intravenously at doses which ...

The long-term replacement therapy with the dopamine (DA) precursor 3,4-dihydroxy-l-phenylalanine (L-DOPA) is a milestone in the treatment of Parkinsons disease (PD). Although this drug precursor can be metabolized into the active neurotransmitter DA throughout the brain, its therapeutic benefit is due to restoring extracellular DA levels within the dorsal striatum, which lacks endogenous DA as a consequence of the neurodegenerative process induced by the disease. In the early phases of PD, L-DOPA treatment is able to restore both long-term depression (LTD) and long-term potentiation (LTP), two major forms of corticostriatal synaptic plasticity that are altered by dopaminergic denervation. However, unlike physiological DA transmission, this therapeutic approach in the advanced phase of the disease leads to abnormal peaks of DA, non-synaptically released, which are supposed to trigger behavioural sensitization, namely L-DOPA-induced dyskinesia. This condition is characterized by a loss of ...

The role of dopamine in plasticity at glutamatergic synapses in the striatum is central to our understanding of basal ganglia functions and dopamine-dependent reward mechanisms. Long-term potentiation (LTP) and long-term depression (LTD) at these synapses are thought to be dependent on D1 and D2 dopamine receptors, respectively. However, the mechanisms of LTP and LTD in the striatum are controversial. Using brain slices from transgenic mice, Shen et al. show that LTP and LTD can occur in both D1- and D2-expressing neurons but with different molecular mechanisms. Dopaminergic modulation of plasticity is receptor and cell-type specific. The findings suggest that the control of bidirectional plasticity is not exerted through a monolithic mechanism, as previously asserted, but by cell-type-specific mechanisms depending on the subtype of dopamine receptor expressed.. W. Shen, M. Flajolet, P. Greengard, D. J. Surmeier, Dichotomous dopaminergic control of striatal synaptic plasticity. Science 321, ...