The ability of phencyclidine (PCP), amphetamine and other substances to stimulate dopamine release from and inhibit dopamine uptake into rat striatal synaptosomes was examined in a continuous superfusion system. Inhibition of uptake was measured by determining inhibition of [3H]dopamine displacement by unlabeled dopamine ([1H]dopamine). The displacement of [3H]dopamine by 10(-7) M [1H]dopamine was temperature- and sodium-sensitive and calcium-independent. [1H]Dopamine was an order of magnitude more potent than serotonin or norepinephrine in displacing [3H]dopamine. The concentrations of reserpine required to inhibit [3H]dopamine uptake and [3H]dopamine displacement by [1H]dopamine were similar. Nomifensine, benztropine, PCP and amphetamine also inhibited the displacement of [3H]dopamine by [1H]dopamine at concentrations which have been shown previously to inhibit the uptake of [3H]dopamine, suggesting that the mechanism behind displacement and uptake are very similar. PCP, at 10(-7) to 10(-5) M, ...

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TY - JOUR. T1 - Acute cyclosporine renal dysfunction reversed by dopamine infusion in healthy subjects. AU - Conte, G.. AU - Dal Canton, A.. AU - Sabbatini, M.. AU - Napodano, P.. AU - De Nicola, L.. AU - Gigliotti, G.. AU - Fuiano, G.. AU - Testa, A.. AU - Esposito, C.. AU - Russo, D.. AU - Andreucci, V. E.. PY - 1989. Y1 - 1989. N2 - Up to now, no studies have been performed in normal humans to investigate the role of renal hemodynamic abnormalities in relation to acute-cyclosporin A (CsA) renal dysfunction and to verify whether the specific renal vasodilator, dopamine, can counteract these abnormalities. Eight normal subjects were examined both (A) after oral CsA (12 mg/kg body wt) and (B) after oral CsA + dopamine infusion (2 mg/kg body wt/min), under water diuresis. Both in protocols A and in B, four basal renal clearances were performed before CsA and every twenty minutes for four hours after CsA administration. In protocol A, after CsA, insulin (GFR) and PAH clearance (RPF) fell by up to ...

TY - JOUR. T1 - Dopamine and the mechanisms of cognition. T2 - Part I. A neural network model predicting dopamine effects on selective attention. AU - Servan-Schreiber, David. AU - Bruno, Randy M.. AU - Carter, Cameron S.. AU - Cohen, Jonathan D.. PY - 1998/5/15. Y1 - 1998/5/15. N2 - Background: Dopamine affects neural information processing, cognition, and behavior; however, the mechanisms through which these three levels of function are affected have remained unspecified. We present a parallel distributed processing model of dopamine effects on neural ensembles that accounts for effects on human performance in a selective attention task. Methods: Task performance is stimulated using principles and mechanisms that capture salient aspects of information processing in neural ensembles. Dopamine effects are simulated as a change in gain of neural assemblies in the area of release. Results: The model leads to different predictions as a function of the hypothesized location of dopamine effects. ...

The regulation of dopamine (DA) synthesis in rat mesocortical DA neurons was studied and compared with DA synthesis in nigrostriatal DA neurons. The increase in striatal DA content caused by γ-butyrolactone (GBL) was reversed by activation of nerve-terminal DA autoreceptors by apomorphine. In contrast, the GBL-induced increase in prefrontal cortical DA was unaffected by DA agonists. By using the accumulation of dopa after the administration of the dopa decarboxylase inhibitor Ro4-4602 as an index of DA synthesis, it was demonstrated that the increase in striatal DA following GBL was due to an acceleration of DA synthesis. In contrast, GBL did not increase cortical dopa accumulation. However, GBL completely prevented the rapid decline of DA seen following α-methyltyrosine treatment, indicating that DA turnover had been inhibited in the mesocortical neurons, as has been previously demonstrated with other DA neurons. The monoamine oxidase inhibitor pargyline increased both striatal and cortical ...

TY - JOUR. T1 - Striatal dopamine release during unrewarded motor task in human volunteers. AU - Badgaiyan, Rajendra D.. AU - Fischman, Alan J.. AU - Alpert, Nathaniel M.. PY - 2003/8/6. Y1 - 2003/8/6. N2 - Striatal dopamine is associated with the processing of rewarded motor tasks. Its involvement in mediating unrewarded tasks is, however, unclear. We used a recently developed PET technique to dynamically measure the rate of displacement of a dopamine receptor ligand raclopride in healthy volunteers performing a finger opposition task. Rapid displacement of the ligand from the posterior putamen and the caudate immediately after the task initiation suggested striatal dopamine release during task performance. Since dopamine release was observed in the striatal areas that are implicated in unrewarded tasks by neuroimaging studies, the results demonstrate that the PET method can be used to extend the findings of conventional neuroimaging techniques, that do not provide information about signal ...

In this report we demonstrate for the first time that activation of the dopamine 1/5 receptors results in increased skeletal muscle cAMP, increased non-atrophying muscle mass and reduced atrophy-induced loss of muscle mass and force production. By using knockout mice to differentiate the effects of activation of the dopamine 1 receptor from that of the dopamine 5 receptor, we demonstrate that both the dopamine 1 and dopamine 5 receptors mediate the anti-atrophy effects of the dopamine 1/5 receptor selective agonist SKF 81297. Genetic removal of the dopamine 1 receptor (with maintenance of the dopamine 5 receptor) results in a complete loss of the SKF 81297 mediated EDL mass/force preservation, data consistent with the idea that the dopamine 1 receptor mediates the effects of SKF 81297. In contrast, genetic removal of the dopamine 5 receptor (with maintenance of the dopamine 1 receptor) resulted in a partial loss of SKF 81297 mediated EDL mass/force preservation, data that is inconsistent with ...

TY - JOUR. T1 - N-methyl-d-aspartic acid biphasically regulates the biochemical and electrophysiological response of A10 dopamine neurons in the ventral tegmental area. T2 - in vivo microdialysis and in vitro electrophysiological studies. AU - Wang, Ting. AU - OConnor, William T.. AU - Ungerstedt, Urban. AU - French, Edward D.. PY - 1994/12/15. Y1 - 1994/12/15. N2 - The effects of local perfusion of the ventral tegmental area (VTA) with N-methyl-d-aspartic acid (NMDA) on extracellular dopamine concentrations in the nucleus accumbens were investigated by using in vivo microdialysis in halothane anaesthetized rats. The electrophysiological response of VTA dopamine neurons to NMDA were also assessed in an in vitro rat brain slice preparation. In both preparations NMDA elicited a biphasic response. Exposure of the VTA to low doses of NMDA (, 100 μM) elicited increases in dialysate dopamine levels in the nucleus accumbens and increases in the firing rate of VTA dopamine neurons. Larger doses (, 100 ...

The effect of systemic administration of desmethylimipramine (DMI), an inhibitor of the noradrenaline (NA) reuptake carrier, and of GBR 12909, an inhibitor of the dopamine (DA) reuptake carrier, on the in vivo extracellular concentrations of dopamine (DA) was studied by transcerebral dialysis in the prefrontal cortex and in the dorsal caudate of freely moving rats. In the NA-rich prefrontal cortex only DMI increased extracellular DA concentrations whereas in the dorsal caudate only GBR 12909 was effective. Haloperidol increased extracellular DA concentrations more effectively in the dorsal caudate than in the prefrontal cortex. Pretreatment with DMI, which failed to modify the effect of haloperidol in the dorsal caudate, potentiated its action in the prefrontal cortex. The reverse was obtained after GBR 12909 + haloperidol in the two areas. 6-hydroxydopamine lesioning of the dorsal NA bundle prevented the ability of DMI to increase DA concentrations. The results suggest that reuptake into NA ...

Dopamine has been reported to rise and fall with ∼15-fold slower kinetics in the SNc than in the striatum (Chen and Rice, 2001). The extended presence of dopamine has been interpreted to result in paracrine, or volume-based, transmission. In the midbrain, [DA]o peaked with the same latency as in the dorsal striatum. There was less than a twofold difference in the half-width of dopamine transient in the midbrain compared with that in the striatum. This small difference most likely represents an increase in the total number of dopamine transporters in the striatum. The major difference between the VTA and striatum was the total amount of dopamine released. While the difference in release may possibly reflect differences in the loading of vesicles in terminals versus dendrites, it more likely reflects the higher density of release sites in the striatum. The present study indicates that release of dopamine from axon and dendrites occurs with a similar time course. Thus these results indicate that ...

Fingerprint Dive into the research topics of Cannabinoid CB,sub,2,/sub, receptors modulate midbrain dopamine neuronal activity and dopamine-related behavior in mice. Together they form a unique fingerprint. ...

There is increased appreciation that dopamine neurons in the midbrain respond not only to reward1 and reward-predicting cues1,2, but also to other variables such as the distance to reward3, movements4-9 and behavioural choices10,11. An important question is how the responses to these diverse variables are organized across the population of dopamine neurons. Whether individual dopamine neurons multiplex several variables, or whether there are subsets of neurons that are specialized in encoding specific behavioural variables remains unclear. This fundamental question has been difficult to resolve because recordings from large populations of individual dopamine neurons have not been performed in a behavioural task with sufficient complexity to examine these diverse variables simultaneously. Here, to address this gap, we used two-photon calcium imaging through an implanted lens to record the activity of more than 300 dopamine neurons from the ventral tegmental area of the mouse midbrain during a complex

Polymorphisms in the gene for the α5 nicotinic acetylcholine receptor (nAChR) subunit are associated with vulnerability to nicotine addiction. However, the underlying normal functions of α5-containing nAChRs in the brain are poorly understood. Striatal dopamine (DA) transmission is critical to the acquisition and maintenance of drug addiction and is modulated strongly by nicotine acting at heteromeric β2-containing (β2*) nAChRs. We explored whether α5 subunits, as well as α4, α6, and β3 subunits, participate in the powerful regulation of DA release probability by β2* nAChRs in nucleus accumbens (NAc) core and in dorsal striatum [caudatoputamen (CPu)]. We detected evoked dopamine release using fast-scan cyclic voltammetry at carbon-fiber microelectrodes in striatal slices from mice with deletions of α4, α5, α6, or β3 subunits. We show that the nAChR subtypes that dominantly regulate dopamine transmission depend critically upon α5 subunits in the dorsal CPu in α4α5(non-α6)β2-nAChRs but

Reinforcement systems are believed to drive synaptic plasticity within neural circuits that store memories. Recent evidence from the fruit fly suggests that anatomically distinct dopaminergic neurons ultimately provide the key instructive signals for both appetitive and aversive learning. This dual role for dopamine overturns the previous model that octopamine signalled reward and dopamine punishment. More importantly, this anatomically segregated double role for dopamine in reward and aversion mirrors that emerging in mammals. Therefore, an antagonistic organization of distinct reinforcing dopaminegic neurons is a conserved feature of brains. It now seems crucial to understand how the dopaminergic neurons are controlled and what the released dopamine does to the underlying circuits to convey opposite valence. © 2013 Elsevier Ltd.

Excess dopamine and abnormal dopamine synthesis cause the positive symptoms of schizophrenia, but does this dysfunction also account for the negative and cognitive symptoms seen in this disorder? Here, get an overview of dopamine dysfunction and find out why this treatment target may be limited for patients with schizophrenia.

BACKGROUND: Recreational and medicinal drugs need to be evaluated with regard to addictive properties. Reinforcing effects contribute to a drugs abuse liability and predict subsequent use. The neurotransmitter dopamine plays an important role in modulating reinforcing effects in the reward circuitry of the brain. Most drugs of abuse increase extrasynaptic ... read more dopamine by stimulating release from synaptic vesicles, by blocking reuptake by binding to the dopamine transporter or by indirectly increasing dopamine via interactions with other neurotransmitter systems. This increase in dopamine is necessary, but not sufficient to produce reinforcing effects such as a feeling of high. Molecular imaging techniques such as positron emission tomography (PET) allow the tracking of drugs in vivo and moreover, can provide an indirect measure of drug-induced dopaminergic responses. OBJECTIVE: The present paper (1) investigates pharmacokinetics and potency to increase dopamine of commonly used ...

Title:The Dopamine D,sub,2,/sub, and Adenosine A,sub,2A,/sub, Receptors: Past, Present and Future Trends for the Treatment of Parkinsons Disease. VOLUME: 21 ISSUE: 27. Author(s):M. Jorg, P.J. Scammells and B. Capuano. Affiliation:Monash Institute of Pharmaceutical Sciences, 381 Royal Parade, Parkville, Victoria 3052, Australia.. Keywords:Adenosine A2A receptor antagonist, bivalent ligand, dopamine, dopamine D2 receptor agonist, G protein-coupled receptor, levodopa, non-dopaminergic drug, Parkinsons disease.. Abstract:Herein, we present an overview of the historic development of drugs for the treatment of Parkinsons disease as well as prospective novel treatment forms based on targeting the dopamine and adenosine receptors. The review includes the development of levodopa, a precursor of the neurotransmitter dopamine, which to date is the most commonly prescribed and most effective drug for controlling the motor symptoms of Parkinsons disease, to more recent studies of the adenosine receptor; ...

TY - JOUR. T1 - Dopamine toxicity in neuroblastoma cells. T2 - Role of glutathione depletion by L-BSO and apoptosis. AU - Stokes, Alan H.. AU - Lewis, Denise Y.. AU - Lash, Lawrence H.. AU - Gray Jerome, W.. AU - Grant, Ken W.. AU - Aschner, Michael. AU - Vrana, Kent E.. N1 - Funding Information: This work was supported by grants GM 38931 (KEV) and T32 DA 07246 (AHS). PY - 2000. Y1 - 2000. N2 - Dopamine (DA), while an essential neurotransmitter, is also a known neurotoxin that potentially plays an etiologic role in several neurodegenerative diseases. DA metabolism and oxidation readily produce reactive oxygen species (ROS) and DA can also be oxidized to a reactive quinone via spontaneous, enzyme-catalyzed or metal-enhanced reactions. A number of these reactions are cytotoxic, yet the precise mechanisms by which DA leads to cell death remain unknown. In this study, the neuroblastoma cell line, SK-N-SH, was utilized to examine DA toxicity under varying oxidant states. Cells pretreated with the ...

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Feeding induced by food deprivation is accompanied by an increased production of the dopamine metabolite 3,4-dihydroxyphenylacetic acid in the brains of rats. This neurochemical change occurs in the nucleus accumbens, the posterior hypothalamus, and the amygdala but not in other dopaminergic nerve terminal fields such as the corpus striatum. These results indicate that the release of dopamine from particular groups of central neurons is increased during feeding and suggest that anatomically distinct subgroups of central dopaminergic neurons serve different roles in the regulation of food intake. ...

In contrast, in neurons projecting to dopamine neurons, dendrites curved and coursed circuitously or turned inward toward the soma (Figure 6K). Furthermore, spines of inputs to GABAergic neurons were evenly. spaced and were of similar size. In contrast, inputs to dopamine neurons had uneven spines and varicosities, and their dendrites were irregular in contour (Figures 6D and 6H, inset). These results suggest that, whereas neurons projecting to GABAergic neurons are click here consistent with typical medium spiny neurons, neurons projecting to dopaminergic neurons have significantly different morphologies. We make two conclusions from these data: First, striatal neurons do project monosynaptically to dopamine neurons; and second, our technique is capable of revealing exquisite, cell-type-specific connectivity. Whereas SNc dopamine neurons receive the most input from the DS, VTA dopamine Buparlisib neurons receive the most input from the Acb (Figure 3). Although heterogeneity of the Acb was ...

TY - JOUR. T1 - Use of dopamine in the ICU. Hope, hype, belief and facts. AU - Girbes, A. R.J.. AU - Smit, A. J.. PY - 1997/1/1. Y1 - 1997/1/1. N2 - Dopamine is frequently administered in the ICU to critically-ill patients. The widespread use of dopamine does not only involve states of distributive and cardiogenic (imminent) shock, but also prophylaxis for deterioration and/or improvement of kidney- and bowel perfusion. Although many studies have shown an increase of renal- and (in some studies) improvement of splanchnic circulation, well controlled studies have failed to demonstrate a better outcome with respect to renal function and/or survival of prophylactic dopamine administration. Furthermore, evidence exists that norepinephrine is more efficacious in fluid resuscitated septic shock patients to restore blood pressure than dopamine, without jeopardizing the renal function. It is concluded that the widespread use of dopamine in the ICU should be reassessed.. AB - Dopamine is frequently ...

The focus of my research lab is on the neurochemical messenger dopamine and its role in brain function. Specifically, my research has explored how drugs (e.g., amphetamine and methamphetamine) impact dopamine mediated behaviors and cellular signaling molecules implicated in memory formation. More recent research elucidated amphetamines cellular mechanism of action on dopamine neurotransmission. As a faculty member at EWU, my lab utilizes the technique of voltammetry which provides one the ability to monitor the activity of specific molecules (e.g., dopamine) in the brain. Future directions are to continue to investigate dopamine function, how drugs impact these processes, and dopamine dysfunction related to pathological conditions such as Parkinsons disease.. Publications:. Amphetamine Paradoxically Augments Exocytotic Dopamine Release and Phasic Dopamine Signals. Methamphetamine neurotoxicity decreases phasic, but not tonic, dopaminergic signaling in the rat striatum. Effect of ...

Duke University Medical Center researchers have discovered a new mechanism by which chronically high levels of the neurotransmitter dopamine exert their effects on the brain.

Genetic and pharmacological reductions of VMAT2 result in lower tissue levels of striatal dopamine (Fon et al., 1997; Takahashi et al., 1997; Wang et al., 1997; Mooslehner et al., 2001). Consistent with previous reports, analysis of dopamine in our VMAT2 transgenic animals showed significantly reduced striatal dopamine levels (Fig. 1 D), as well as DOPAC and HVA (data not shown). Striatal dopamine levels remain unchanged in the VMAT2 WT mice up to 12 months of age. In contrast, dopamine levels continue to decline in the aged VMAT2 LO animals, as seen previously in VMAT2 LO mice that are α-synuclein null (Colebrooke et al., 2006) (Fig. 1 E). These reductions are accompanied by an increase in the ratios of dopamine metabolites to dopamine in the aged VMAT2 LO mice (Fig. 2 A,B), suggesting an increase in dopamine turnover (Zigmond et al., 2002). This increase appears to be a result of the age-dependent loss of striatal dopamine, in that the levels of DOPAC and HVA remain unchanged in the aged ...

TY - JOUR. T1 - Does Dopamine Act at Dopamine Receptors in the Ciliary Epithelia?. AU - Wax, M. B.. PY - 1993/3/1. Y1 - 1993/3/1. UR - http://www.scopus.com/inward/record.url?scp=0027526563&partnerID=8YFLogxK. UR - http://www.scopus.com/inward/citedby.url?scp=0027526563&partnerID=8YFLogxK. U2 - 10.1006/exer.1993.1048. DO - 10.1006/exer.1993.1048. M3 - Editorial. C2 - 8472793. AN - SCOPUS:0027526563. VL - 56. SP - 371. EP - 373. JO - Experimental Eye Research. JF - Experimental Eye Research. SN - 0014-4835. IS - 3. ER - ...

Dopamine signaling is conserved across all animal species and has been implicated in the disease process of many neurological disorders, including Parkinsons disease (PD). The primary neuropathology in PD involves the death of dopaminergic cells in the substantia nigra (SN), an anatomical region of the brain implicated in dopamine production and voluntary motor control. Increasing evidence suggests that the neurotransmitter dopamine may have a neurotoxic metabolic product (DOPAL) that selectively damages dopaminergic cells. This study was designed to test this theory of oxidative damage in an animal model of Parkinsons disease, using a transgenic strain of zebrafish with fluorescent labeling of cells that express the dopamine transporter. The pretectum and ventral diencephalon exhibited reductions in cell numbers due to L-DOPA treatment while reticulospinal neurons that do not express the DAT were unaffected, and this was partially rescued by monoamine oxidase inhibition. Consistent with the ...

The striatum, which is the major component of the basal ganglia in the brain, is regulated in part by dopaminergic input from the substantia nigra. Severe movement disorders result from the loss of striatal dopamine in patients with Parkinsons disease. Rats with lesions of the nigrostriatal dopamine pathway caused by 6-hydroxydopamine (6-OHDA) serve as a model for Parkinsons disease and show alterations in gene expression in the two major output systems of the striatum to the globus pallidus and substantia nigra. Striatopallidal neurons show a 6-OHDA-induced elevation in their specific expression of messenger RNAs (mRNAs) encoding the D2 dopamine receptor and enkephalin, which is reversed by subsequent continuous treatment with the D2 agonist quinpirole. Conversely, striatonigral neurons show a 6-OHDA-induced reduction in their specific expression of mRNAs encoding the D1 dopamine receptor and substance P, which is reversed by subsequent daily injections of the D1 agonist SKF-38393. This ...

Low dopamine levels can lead to a lack of motivation, fatigue, addictive behavior, mood swings, and memory loss. Learn how to increase dopamine naturally. Dopamine is a major neurotransmitter thats […]. The post How to Increase Dopamine Naturally appeared first on Be Brain Fit.. ...

Research reported by scientists from the University of California-San Francisco (UCSF) has shown that, in a rat model, Ritalin (methylphenidate) boosts both the ability to focus on tasks and the speed of learning by increasing the activity of the neurotransmitter dopamine through mechanisms involving two distinct dopamine receptors in the amygdala region of the brain. We found that a dopamine receptor, known as the D2 receptor, controls the ability to stay focused on a task--the well-known benefit of Ritalin, said Dr. Patricia Janak, co-senior author of the paper. But we also discovered that another dopamine receptor, D1, underlies learning efficiency. Since we now know that Ritalin improves behavior through two specific types of neurotransmitter receptors, the finding could help in the development of better targeted drugs, with fewer side effects, to increase focus and learning, said Dr. Antonello Bonci, the other co-senior author of the article. The research assessed the ability of rats ...

In this study the investigators propose that the retina itself in albinism is deficient in dopamine, and vision improvement will occur as a result of improved retinal function in response to the deficient neurotransmitter dopamine. This study has a pretest-posttest design in order to determine if improvement in vision is in response to replacement of deficiency (dopamine). The ERG testing and OCT will be critical determinants to confirm vision improvement as a result of improved retinal function, but are not primary outcome data. Main outcome measures will be collected at pre-treatment, 1 month, 3 months, and 4 months. Change in visual acuity as measured in logMAR by Snellen or SVEP after 3 months of treatment is the primary outcome. Patients include OCA1a patients, OCA1b, OCA2, and unclassified OCA. OCA1a patients clinically are known to have the worst vision, and physiologically have the lowest (or absent) levels of tyrosinase function (Dopamine Production). All patients will be treated with ...

The dopamine biosynthetic machinery of intact synaptosomes of rat striatum showed a 5-fold increase in development from 3-day-old neonates to adults, and it was fully developed between 2-3 weeks after birth. Concurring with this development was the appearance 2 weeks after birth of a regulatory mechanism(s) through which amphetamine in vivo induced an inhibition of dopamine biosynthesis. The inhibition was not appreciably reversed when haloperidol, in addition to amphetamine, was administered. ...

However, recently, in a number of clinical trials with dopaminergic agents have also been conducted and their beneficial effects for controlling pain51 and depression19 have been demonstrated. A recent study investigated whether or not pain-related behavioural depression is mediated by activation of endogenous κ-opioid systems and subsequent depression of mesolimbic dopamine release.52 That study found a crucial role of dopamine neurotransmission in terms of pain-related depression of behaviour, pain-related depression of mesolimbic dopamine release and role of endogenous dynorphin/κ-opioid receptor systems: 1) the acid noxious stimulus also depressed extracellular levels of the neurotransmitter dopamine in nucleus accumbens; supporting the fact that depression of mesolimbic dopamine release may contribute to negative affective dimensions of pain; 2) acid-induced depression of dopamine release was blocked by both NSAID and opioid analgesics, indicating the potential relationship of opioid with ...

PubMed journal article: Paraquat induces selective dopaminergic nigrostriatal degeneration in aging C57BL/6 mice. Download Prime PubMed App to iPhone, iPad, or Android

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Author: Lloyd, K et al.; Genre: Poster; Published online: 2015-06; Title: Pre-response dopamine transients in the nucleus accumbens

Abstract. Parkinsons disease (PD) results from progressive degeneration of dopaminergic neurons. Most PD cases are sporadic, but some have pathogenic mutation in the individual genes. Mutation of the leucine-rich repeat kinase-2 (LRRK2) gene is associated with familial and sporadic PD, as exemplified by G2019S substitution. While constitutive expression of mutant LRRK2 in transgenic mice fails to induce neuron death, transient expression of the disease gene by viral delivery causes a substantial loss of dopaminergic neurons in mice. To further assess LRRK2 pathogenesis, we created inducible transgenic rats expressing human LRRK2 with G2019S substitution. Temporal overexpression of LRRK2G2019S in adult rats impaired dopamine reuptake by dopamine transporter (DAT) and thus enhanced locomotor activity, the phenotypes that were not observed in transgenic rats constitutively expressing the gene throughout life time. Reduced DAT binding activity is an early sign of dopaminergic dysfunction in ...

Dopamine (DA) release varies within subregions and local environments of the striatum, suggesting that controls intrinsic and extrinsic to the DA fibers and terminals regulate release. While applying fast-scan cyclic voltammetry and using tonic and phasic stimulus trains, we investigated the regulation of DA release in the dorsolateral to ventral striatum. The ratio of phasic-to-tonic-evoked DA signals varied with the average ongoing firing frequency, and the ratio was generally higher in the nucleus accumbens (NAc) compared with the dorsolateral striatum. At the normal average firing frequency, burst stimulation produces a larger increase in the DA response in the NAc than the dorsolateral striatum. This finding was comparable whether the DA measurements were made using in vitro brain slices or were recorded in vivo from freely moving rodents. Blockade of the dopamine transporters and dopamine D2 receptors particularly enhanced the tonic DA signals. Conversely, blockade of nicotinic ...

The effects of Pro-Leu-GlyNH2 (PLG), administered i.c.v. in doses of 3.5, 35, 350 and 3500 pmol, were studied on the α-MPT-induced disappearance of catecholamines in microdissected rat brain nuclei. PLG, dose-dependently, increased dopamine disappearance in the nucleus caudatus and globus pallidus, whereas a decrease in dopamine disappearance was observed in ... read more the nucleus dorsomedialis. Noradrenaline disappearance was decreased in the medial septal nucleus, anterior hypothalamic area and lateral amygdala. A tendency towards an increase in noradrenaline disappearance was observed in the nucl. supraopticus. These data show that PLG has a central site of action. The effects of PLG on dopamine disappearance are comparable to those previously found with vasopressin, while the effects of PLG on noradrenaline utilization show a striking similarity with those previously obtained with oxytocin. show less ...

Modelling ischaemia in vitro: Effects of temperature and glucose concentration on dopamine release evoked by oxygen and glucose depletion in a mouse brain ...

The opiates bind to the opiate receptors in the brain, increasing a dopamine release, but once gone, there is an ever-increasing need for more opiate (or other drug) to induce the same dopamine-high. This is what causes drug addicts to resort to ever increasing, negative behaviors to get their next fix. The dopamine high is that desirable.. In experiments conducted with mice, when the same nerve bundle that causes an opiate release was stimulated when they pressed a lever, the mice, left to their own devices, would press the lever thousands of times in an hour, due to the pleasurable feelings the dopamine would induce. A later experiment (conducted unethically on a human being) showed a similar response. Over the course of three hours, a person would press a button which triggered a dopamine dump thousands of times to get an immense emotional boost.. We get little dopamine dumps in our brains with less destructive behaviors - like making money, having sex, and even winning a video game, but ...

Menegas et al. used a combination of a powerful anatomical technique called CLARITY (Chung et al., 2013) and light-sheet microscopy to map the input and output projections of dopamine neurons in an intact mouse brain. First, subsets of dopamine neurons were classified according to which of eight regions - medial pre-frontal cortex, orbitofrontal cortex, central amygdala, globus pallidus, ventral striatum, dorsal striatum, tail of the striatum, or lateral habenula - they projected onto. Next, a given subset, based on its projection target, was infected to express two proteins (avian retroviral receptor and rabies virus envelop glycoprotein). Then, three weeks later, a modified rabies virus was injected into the dopamine neurons. This virus spreads retrogradely and labels neurons projecting to the dopamine neurons with green fluorescent protein. Menegas et al. had to develop a suite of new data acquisition and analysis tools to map the 3D position of the fluorescently labeled neurons and align ...

from rat brain tissue suggesting affinity at the dopamine transporter and 5-HT2 receptor sites respectively. Voltammetric studies in rat accumbens brain slices revealed that 5-APB slowed dopamine reuptake, and at high concentrations caused reverse transport of dopamine. 5-APB also caused vasoconstriction of rat aorta, an effect antagonized by the 5-HT2A receptor antagonist ketanserin, and caused contraction of rat stomach fundus, which was reversed by the 5-HT2B receptor antagonist RS-127445. These data show that 5-APB interacts with the dopamine transporter and is an agonist at the 5-HT2A and 5-HT2B receptors in the rat. Thus 5-APBs pharmacology is consistent with it having both stimulant and hallucinogenic properties. In addition, 5-APBs activity at the 5-HT2B receptor may cause cardiotoxicity.. ...

ENP team leader Luc Maroteaux and coll determine to unravel links between serotonin and dopamine systems in development and pathophysiological situations. Cocaïne, a powerfully addictive stimulant drug because of the changes it creates in the brain after repeated use, is known to increase levels of the brain dopamine.

Controlled Release of Dopamine from a Polymeric Brain Implant: In Vivo Characterization Matthew J. During, MD, FRACP,t, Andrew Freese, BA,S§, Bernhard A. Sabel, PhDJI W. Mark Saltzrnan, PhD,$§ Arie1 Deutch, PhD,* Robert H. Roth, PhD,X and Robert Langer, ScDS§ Intracerebrai microdialysiswas used to evaiuate the long-term in vivo release of dopamine from ethylene-vinylacetate (EVAddopamine copolymer matrix discs for up to 65 days followingstriatai implantation. Dopamine release occurred through a single cavity present on one side of the disc, which was otherwise fdly coated with an additionai, imperme&le layer of EVAc. At 20 days following implantation of the device, extracelldar concentrations of dopamine within the striatum reached micromolar levels, over 200-fold greater than contro1vaiues. Release of dopamine was shown to be stable and maintained for the 2-month duration of the experiment. Histological examination confirmed the biocompatible nature of the implant. There are potential ...

SCIENTIFIC SUMMARY The project will, in a sample of cocaine-dependent (CD) and healthy control (HC) subjects, use administration of Corticorelin, a synthetic form of corticotropin releasing factor (CRF)and PET imaging to assess dopamine (DA) transmission in addiction. We will use [11C]-(+)-PHNO PET to measure striatal DA receptor binding on two occasions: 1) following corticorelin administration and 2) following saline. The change in receptor binding between the two occasions (i.e., displacement of [11C]-(+)-PHNO by endogenous DA) will index DA release.. SUBJECTS CD subjects will meet DSM-IV criteria for abuse or dependence and be ~10d cocaine abstinent at the time of PET. HC will be recruited to match CD on age, sex, education, and cigarette smoking.. PRIMARY OUTCOME MEASURES We will measure [11C]-(+)-PHNO binding on two occasions (corticorelin, saline), with the difference between conditions indexing dopamine release; this measure will then be compared between cocaine-dependent and control ...

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 ...

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 ...

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 ...

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 ...