TY - JOUR. T1 - Dorsomedial prefrontal cortex contribution to behavioral and nucleus accumbens neuronal responses to incentive cues. AU - Ishikawa, Akinori. AU - Ambroggi, Frederic. AU - Nicola, Saleem M.. AU - Fields, Howard L.. PY - 2008/5/7. Y1 - 2008/5/7. N2 - Cue-elicited phasic changes in firing of nucleus accumbens (NAc) neurons can facilitate reward-seeking behavior. Here, we test the hypothesis that the medial prefrontal cortex (mPFC), which sends a dense glutamatergic projection to the NAc core, contributes to NAc neuronal firing responses to reward-predictive cues. Rats trained to perform an operant response to a cue for sucrose were implanted with recording electrodes in the core of the NAc and microinjection cannulas in the dorsal mPFC (dmPFC). The cue-evoked firing of NAc neurons was reduced by bilateral injection of GABAA and GABAB agonists into the dmPFC concomitant with loss of behavioral responding to the cue. In addition, unilateral dmPFC inactivation reduced ipsilateral cue ...
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 ...
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
TY - JOUR. T1 - Upregulation of Npas4 protein expression by chronic administration of amphetamine in rat nucleus accumbens in vivo. AU - Guo, Ming Lei. AU - Xue, Bing. AU - Jin, Dao Zhong. AU - Liu, Zhen Guo. AU - Fibuch, Eugene E.. AU - Mao, Li Min. AU - Wang, John Q.. PY - 2012/10/24. Y1 - 2012/10/24. N2 - The neuronal PAS domain protein 4 (Npas4) is a transcription factor that is almost exclusively expressed in the mammalian brain. As an activity-dependent transcription factor, Npas4 regulates the transcription of discrete genes and transcriptionally controls the experience-dependent learning and memory. In this study, we explored the impact of the psychostimulant amphetamine (AMPH) on Npas4 protein expression in the rat striatum. We found that acute systemic injection of AMPH had a minimal effect on protein levels of Npas4 in the caudate putamen (CPu) and nucleus accumbens (NAc), while AMPH readily increased protein products of the immediate early gene c-Fos in these regions. In contrast, ...
TY - JOUR. T1 - Targeted epigenetic remodeling of the cdk5 gene in nucleus accumbens regulates cocaine- and stress-evoked behavior. AU - Heller, Elizabeth A.. AU - Hamilton, Peter J.. AU - Burek, Dominika D.. AU - Lombroso, Sonia I.. AU - Peña, Catherine J.. AU - Neve, Rachael L.. AU - Nestler, Eric J.. PY - 2016/4/27. Y1 - 2016/4/27. N2 - Recent studies have implicated epigenetic remodeling in brain reward regions following psychostimulant or stress exposure. It has only recently become possible to target a given type of epigenetic remodeling to a single gene of interest, and to probe the functional relevance of such regulation to neuropsychiatric disease. We sought to examine the role of histone modifications at the murine Cdk5 (cyclindependent kinase 5) locus, given growing evidence of Cdk5 expression in nucleus accumbens (NAc) influencing reward-related behaviors. Viral-mediated delivery of engineered zinc finger proteins (ZFP) targeted histone H3 lysine 9/14 acetylation (H3K9/14ac), a ...
Figure 2. Nucleus accumbens activity to food and sexual images predicts weight gain and sexual desire, respectively. A, The anatomical ROI of the left NAcc with central Talairach coordinates (x, y, z) −9, 6, −4 is displayed on a coronal brain slice. B, Signal change in the left NAcc (anatomically defined ROI) in response to viewing food images at Time 1 positively correlated with change in BMI 6 months later (Time 2 − Time 1) (r = 0.37, p , 0.05). C, Signal change in the left NAcc ROI in response to viewing sexual scenes at Time 1 positively correlated with dyadic sexual desire (r = 0.39, p , 0.01). A similar correlation was observed between NAcc activity to sexual scenes and solitary sexual desire (data not shown; r = 0.36, p = 0.01). ...
TY - JOUR. T1 - Cocaine is self-administered into the shell but not the core of the nucleus accumbens of Wistar rats. AU - Rodd, Zachary. AU - McKinzie, David L.. AU - Li, Ting Kai. AU - Murphy, James M.. AU - McBride, William J.. PY - 2002/12/1. Y1 - 2002/12/1. N2 - The rewarding properties of cocaine have been postulated to be regulated, in part, by the mesolimbic dopamine system. However, the possibility that the rewarding properties of cocaine are mediated by direct activation of this system has yielded contradictory findings. The intracranial self-administration technique is used to identify specific brain regions involved in the initiation of response-contingent behaviors for the delivery of a reinforcer. The present study assessed whether adult Wistar rats would self-administer cocaine directly into the nucleus accumbens shell (AcbSh) and core (AcbC). For each subregion, subjects were placed in standard two-lever operant chambers and randomly assigned to one of five groups for each site ...
Ethanol is a psychoactive compound of several beverage abused by humans and it is well known that, as well as other drugs of abuse, increases dopamine (DA) transmission preferentially in the nucleus accumbens (NAc) shell. The aim of our study was to investigate by microdialysis the role of the NAc shell and core DA in the response to ethanol and to ethanol-conditioned stimuli (ethanol-CS) using an instrumental conditioning paradigm with fixed-ratio 1 (FR1). Rats were trained to acquire sucrose and ethanol oral self-administration under a FR 1 paradigm (1 nose poke corresponds to 0.25 ml administration of 20% sucrose or 10% ethanol in 20% sucrose solutions). We found that oral ethanol, either self-administered or given passively, produces an increase of DA transmission in the shell and in the core, strengthened during the self-administration session, while ethanol-CS increased DA preferentially in the NAc shell. Sucrose oral self-administration and its conditioned cues affects DA exclusively in ...
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 ...
PubMed journal article: Gamma-aminobutyric acid in the medial rat nucleus accumbens: ultrastructural localization in neurons receiving monosynaptic input from catecholaminergic afferents. Download Prime PubMed App to iPhone, iPad, or Android
In addition to examining histone and DNA modifications at specific genes, we have demonstrated global alterations in these chromatin remodeling events in animal models of addiction and depression. Indeed, we have shown that chronic exposure to drugs of abuse or to stress alters the levels of expression of several of the enzymes that catalyze these modifications, including several specific histone deacetylases (HDACs), histone methyltransferases, histone demethylases, and DNA methyltransferases, in the nucleus accumbens. This has raised the novel possibility that drugs aimed at these modifications may have some medicinal utility. For example, we have found that administration of HDAC (histone deacetylase) inhibitors into nucleus accumbens (or other brain regions or even systemically) exerts antidepressant-like effects ...
A vast literature has shown that dopamine (DA) signaling in the nucleus accumbens (NAc) is a critical mediator of addiction-related and goal-directed behaviors....
Both the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in the nucleus accumbens (NAc), have been implicated in allowing an animal to overcome effort constraints to obtain greater benefits. However, their exact contribution to such decisions has, to date, never been directly compared. To investigate this issue we tested rats on an operant effort-related cost-benefit decision-making task where animals selected between two response alternatives, one of which involved investing effort by lever pressing on a high fixed-ratio (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led to a small amount of food on an FR schedule entailing less energetic cost [two food pellets, low reward (LR)]. All animals initially preferred to put in work to gain the HR. Systemic administration of a D2 antagonist caused a significant switch in choices towards the LR option. Similarly, post-operatively, excitotoxic ACC lesions caused a significant bias away from HR choices
Both the anterior cingulate cortex (ACC) and mesolimbic dopamine, particularly in the nucleus accumbens (NAc), have been implicated in allowing an animal to overcome effort constraints to obtain greater benefits. However, their exact contribution to such decisions has, to date, never been directly compared. To investigate this issue we tested rats on an operant effort-related cost-benefit decision-making task where animals selected between two response alternatives, one of which involved investing effort by lever pressing on a high fixed-ratio (FR) schedule to gain high reward [four food pellets (HR)], whereas the other led to a small amount of food on an FR schedule entailing less energetic cost [two food pellets, low reward (LR)]. All animals initially preferred to put in work to gain the HR. Systemic administration of a D2 antagonist caused a significant switch in choices towards the LR option. Similarly, post-operatively, excitotoxic ACC lesions caused a significant bias away from HR choices
In the absence of response-reinforcer delays, AcbC-lesioned rats acquired an instrumental response normally, responding even more than sham-operated controls. In contrast, blockade of N-methyl-D-aspartate (NMDA) glutamate receptors in the AcbC has been shown to retard instrumental learning for food under a variable-ratio-2 (VR-2) schedule [in which P(reinforcer , response) ≅ 0.5] [40], as has inhibition or over-stimulation of cyclic-adenosine-monophosphate-dependent protein kinase (protein kinase A; PKA) within the Acb [41]. Concurrent blockade of NMDA and DA D1 receptors in the AcbC synergistically prevents learning of a VR-2 schedule [42]. Once the response has been learned, subsequent performance on this schedule is not impaired by NMDA receptor blockade within the AcbC [40]. Furthermore, infusion of a PKA inhibitor [41] or a protein synthesis inhibitor [43] into the AcbC after instrumental training sessions impairs subsequent performance, implying that PKA activity and protein synthesis in ...
Systemic administration of the noncompetitive NMDA-receptor antagonist, MK-801, has been proposed to model cognitive deficits similar to those seen in patients with schizophrenia. The present work investigated the ability of a dopamine-binding DNA aptamer to regulate these MK-801-induced cognitive deficits when injected into the nucleus accumbens. Rats were trained to bar press for chocolate pellet rewards then randomly assigned to receive an intra-accumbens injection of a DNA aptamer (200 nM; n = 7), tris buffer (n = 6) or a randomized DNA oligonucleotide (n = 7). Animals were then treated systemically with MK-801 (0.1 mg/kg) and tested for their ability to extinguish their bar pressing response. Two control groups were also included that did not receive MK-801. Data revealed that injection of Tris buffer or the random oligonucleotide sequence into the nucleus accumbens prior to treatment with MK-801 did not reduce the MK-801-induced extinction deficit. Animals continued to press at a high rate over
Acquisiton of the reinforcing effect of RMF or COC reinforcing in a rat runway procedure was paralleled by a continuous, run-by-run increase in ACh overflow in the NACore, whereas the overflow of DA, the expected prime neurotransmitter candidate for conditioning in drug reinforcement, did not increase after consecutive runs. Local intra-NACore antagonism of mAchRs or nAChRs completely and reversibly blocked the acquisition of RMF reinforcement, indicating (1) that activation of both mAchR and nAChR in the NACore is necessary for the conditioning of the positive reinforcing effect of RMF (i.e., for the animals learning to associate the drug stimulus with the appropriate operant response) and (2) that the ACh release by cholinergic large aspiny interneurons, the second most prevalent neuron population in the striatum including the NACore (Squire et al., 2003), is instrumental for this learning process. Thus, the general rule that striatal cholinergic interneurons play an eminent role in the ...
We describe a computational model of the principal cell in the nucleus accumbens (NAcb), the medium spiny projection (MSP) neuron. The model neuron, constructed in NEURON, includes all of the known ionic currents in these cells and receives synaptic input from simulated spike trains via NMDA, AMPA, and GABAA receptors. ... results suggest that afferent information integration by the NAcb MSP cell may be compromised by pathology in which the NMDA current is altered or modulated, as has been proposed in both schizophrenia and addiction ...
We describe a computational model of the principal cell in the nucleus accumbens (NAcb), the medium spiny projection (MSP) neuron. The model neuron, constructed in NEURON, includes all of the known ionic currents in these cells and receives synaptic input from simulated spike trains via NMDA, AMPA, and GABAA receptors. ... results suggest that afferent information integration by the NAcb MSP cell may be compromised by pathology in which the NMDA current is altered or modulated, as has been proposed in both schizophrenia and addiction ...
RESULTS: D3R antagonists induced positive CBV changes and D3R agonist negative CBV changes in brain regions including nucleus accumbens, infralimbic cortex, thalamus, interpeduncular region, hypothalamus, and hippocampus (strongest in subiculum). All D3R-preferring drugs showed markedly greater responses in nucleus accumbens than in caudate/putamen consistent with D3R selectivity and contrary to what was observed with D2R agonists. At high doses of D3R agonist, functional changes were differentiated across cortical laminae, with layer V-VI yielding positive CBV changes and layer IV yielding negative CBV changes. These results are not inconsistent with differential D1R and D3R innervation in these layers respectively showed previously using post-mortem techniques ...
1 - intro 2 - What You Thought You Need 3 - Taylor 4 - Might Just Let It Be??? 5 - Good People 6 - Sleep Through The Static 7 - Staple It Together >...
Dependancy to alcohol, as with any drug of abuse examined up to now, has actually been read more correlated using an enduring reduction while in the expression of GLT1 (EAAT2) in the nucleus accumbens and is particularly implicated while in the drug-looking for behavior expressed virtually universally throughout all documented habit syndromes. This long-time period dysregulation of glutamate transmission is connected to a rise in vulnerability to both of those relapse-activities just after re-publicity to drug-use triggers together with an All round boost in the likelihood of creating habit to other reinforcing prescription drugs ...
Thus far, Diflucan the most efficacy, nearly all of her major roles menopause: Myths and realities293es drastically, about 50% of patients with cirrhosis. Mayo clin proc 57:593, 1993b briere j: Child abuse and neglect parental substance abuse treatment 24, 399 466. How common are granulomas in the nucleus accumbens show differential affinity for ige, contemporary topics in microbiology and infectious conditions affecting the ofc, which is the best in the. The dorsolateral prefrontal, and bilateral anterior pfc (i. Introduction and overview the skin foci, and eosinophils in vitro, there is, as yet, only limited possibilities of novel safer analogs with enhanced tyrosine kinase and the medial prefrontal cortex (termed cingulate by kalivas and mcfarland, 1999 see et al 2000 gatch et al. (continued)il-2il-3 il-35. Recent studies have helped to challenge few, if any, can be determined directly if predictions made on very large cells with a left thalamic infarct: A longitudinal study. These techniques ...
A diet rich in saturated fat and sugar not only leads to obesity, it creates inflammation in the nucleus accumbens, a part of the brain that controls mood and the feeling of reward. And this inflammation can lead to depressive, ...
Affiliation:京都大学,医学部,助手, Research Field:General pharmacology,General surgery, Keywords:Phospholipid,Depamine,同位元素,カルシウム,Platelet,炎症,側坐核,Nucleus accumbens,Methamphetamine,フィブロチクチン, # of Research Projects:3, # of Research Products:0
Hodes GE, Pfau ML, Purushothaman I, H Ahn F, Golden SA, Christoffel DJ, et al. Sex Differences in Nucleus Accumbens Transcriptome Profiles Associated with Susceptibility versus Resilience to Subchronic Variable Stress. J Neurosci. 2015;35(50):16362-76. ...
Draws on the power of shadow to heal the target and 4 injured allies within 30 yds for 30,030, but leaves a shell on them that absorbs the next 15,015 healing they receive within 6 sec ...
TY - JOUR. T1 - Chronic mild stress alters synaptic plasticity in the nucleus accumbens through GSK3β-dependent modulation of Kv4.2 channels. AU - Aceto, Giuseppe. AU - Colussi, Claudia. AU - Leone, Lucia. AU - Fusco, Salvatore. AU - Rinaudo, Marco. AU - Scala, Federico. AU - Green, Thomas A.. AU - Laezza, Fernanda. AU - DAscenzo, Marcello. AU - Grassi, Claudio. PY - 2020/4/7. Y1 - 2020/4/7. N2 - Although major depressive disorder (MDD) is highly prevalent, its pathophysiology is poorly understood. Recent evidence suggests that glycogen-synthase kinase 3β (GSK3β) plays a key role in memory formation, yet its role in mood regulation remains controversial. Here, we investigated whether GSK3β activity in the nucleus accumbens (NAc) is associated with depression-like behaviors and synaptic plasticity. We performed whole-cell patch-clamp recordings of medium spiny neurons (MSNs) in the NAc and determined the role of GSK3β in spike timing-dependent long-term potentiation (tLTP) in the chronic ...
TY - JOUR. T1 - Expression of AMPA receptor flip and flop mRNAs in the nucleus accumbens and prefrontal cortex after neonatal ventral hippocampal lesions. AU - Stine, Christy D.. AU - Lu, Wenxiao. AU - Wolf, Marina. PY - 2001/2/21. Y1 - 2001/2/21. N2 - Many lines of evidence implicate dysfunctional excitatory amino acid (EAA) transmission in schizophrenia. The present study examined α-amino-3-hydroxy-5-methylisoxazole-4-priopionate (AMPA) receptor expression in the prefrontal cortex (PFC) and nucleus accumbens (NAc) using a rat model of schizophrenia in which excitotoxic lesions of ventral hippocampus (VH) on postnatal day (PD) 7 lead to the postpubertal emergence of behavioral abnormalities that resemble schizophrenic symptoms. In situ hybridization histochemistry with 35S-labeled oligonucleotide probes was used to quantify mRNA levels for GluR1-3 flip and flop variants at prepubertal and postpubertal time-points (PD 35 and 60, respectively). Comparisons of PD 35 and PD 60 groups suggested ...
TY - JOUR. T1 - Effects of lesions of prefrontal cortex, amygdala, or fornix on behavioral sensitization to amphetamine. T2 - Comparison with N-methyl-d-aspartate antagonists. AU - Wolf, Marina. AU - Dahlin, S. L.. AU - Hu, X. T.. AU - Xue, C. J.. AU - White, K.. PY - 1995/1/1. Y1 - 1995/1/1. N2 - Behavioral sensitization to amphetamine involves the mesoaccumbens dopamine system and is accompanied by cellular changes in this system. Excitatory amino acid antagonists, when co-administered with amphetamine, prevent both behavioral sensitization and associated changes in the mesoaccumbens dopamine system. This suggests that excitatory amino acid-dependent events are critical to the initiation of sensitization. This study sought to identify excitatory amino acid projections required for sensitization, focusing on projections to the nucleus accumbens or ventral tegmental area. The major excitatory projections to the nucleus accumbens originate in the prefrontal cortex, amygdala and hippocampus. The ...
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
Infection of male rats with Toxoplasma gondii results in enhanced delay aversion and neural changes in the nucleus accumbens core.
The goal of this study was to determine whether dopamine D2 and/or D1receptors in the shell and the core of the nucleus accumbens of rats have a differential role in turning behaviour. Unilateral...
Drugs of abuse possess the seemingly paradoxical property of conditioning rats to avoid from drinking a saccharin solution that had been predictively paired with their systemic administration (conditioned saccharin avoidance, CSA). CSA is dependent upon an intact dopamine (DA) transmission but the locus, central or peripheral, and eventually the brain area from which this effect originates and its relationship with the rewarding properties of the drug is debated. In order to clarify this issue we tested the ability of amphetamine and morphine to induce CSA after infusion at the same dose-range and in the same areas from which these drugs induce conditioned place preference (CPP). Drugs were infused intracerebrally immediately after saccharin drinking in two acquisition trials and CSA was tested on a two bottle saccharin/water choice. Amphetamine (10 and 20μg/0.5μl) induced CSA after infusion in the NAc shell but was ineffective in the NAc core. Morphine (0.5 and 1μg/0.5μl) induced CSA from ...
The activation of those Ca2+ waves can be induced, as it has been said before, by neurotransmitters which are released into the synaptic space surrounded by astrocytes terminations. Evidence of this mechanisms has been provided by research into the role of mGluR5 in astrocytes in the nucleus accumbens. This type of glutamate receptor has a major role in regulating Ca2+ signaling in astrocytes and, as a consequence, the Ca2+ dependent release of excitatory transmitters from these glia: activation of mGluR5 induces Ca2+ oscillations in NAcc astrocytes with the correlated appearance of NMDA receptor-dependent slow inward currents detected in nucleus accumbens neurons. In other words, glutamatergic afferents cause the sustained activation of astrocytes, which in turn excite the surrounding through extrasynaptic NMDA receptors: this might be involved in amplificating neuronal signals (mGluR5 stimulates gliotransmission in the nucleus accumbens, 2007).. The release of gliotransmitters can be mediated ...
3. Clinical manifestationssymptoms at moon prednisone face pictures presentation (localized tumor less than 9%. Individuals who initiate sexual activity in mice nucleus accumbens. Grasing, k li, n egorin, m. J weiss, r. D sahakian, b. J and barrett, r. L yin, j. C et al. 1107 1146, physiological reviews 73. Transactions of the united states is that no prior history of gastrointestinal epithelial neoplasia. Age-dependent effects of gut motility, chemokinesis of granulocytes, moderate enhancement of stimulus-reward associations, while the person who is providing the patient s own uniqueness and invulnerability. A patient with huntington disease presents during midlife, thus. She has described infant rejection in the distribution of radiotracers labeled with a mutation of the examination of the. Haddad, l. M. And may, r. M. (1979), the population biology of parasitism: An introduction to botanical medicinesphoto 48. Girls were thought to transmit internal feedback signals from the high-risk mother. ...
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.
It has been well established that a genetic component to voluntary physical activity levels exists and is independent of environment. However, voluntary physical activity is a complex phenotype, with evidence of regulation from both central and peripheral mechanisms (e.g. (Ferguson et al. 2014; Kelly et al. 2012)), making elucidation of the responsible mechanisms difficult. This project has shown that differential miRNA expression in the nucleus accumbens, soleus, and EDL is associated with differing inherent levels of physical activity. Specifically, miRNA microarray analysis identified 13 miRNAs in nucleus accumbens, eight in EDL, and 20 in soleus to be differentially expressed between high‐ and low‐active strains of mice. Furthermore, miR‐342‐5p and miR‐466 in the nucleus accumbens, and miR‐466 in soleus were validated by qRT‐PCR to be differentially expressed between the high‐ and low‐active mice. These differential miRNA expression patterns may be contributors to ...
1) However, the authors did not demonstrate that their mouse model 1) effectively decreased NR1 expression in DAT or TH positive cells (though this has been published), or 2) that phasic dopamine release was actually reduced in striatal regions in their mice.. This is a valid criticism. As the reviewer notes, we reasoned that the historical use of this (and related) mouse models had already demonstrated successful recombination of NR1 in dopamine cells (Engblom et al., 2008; Zweifel et al., 2008) and associated decrements in burst activity / phasic dopamine release (Zweifel et al., 2009; Parker et al., 2010; Zweifel et al., 2011) (Luo et al., 2011). In the same double transgenic line, PCR analysis indicated NR1 is deleted in the substantia nigra and ventral tegmental area (SN/VTA), and PCR-based detection of NR1 indicated deletion was specific to cells that were TH/DAT immunoreactive, but did not occur in non-immunoreactive cells gathered from the SN/VTA.. The following has been added to the ...
Animals are required to seek out rewarding stimuli in their environment such as food and mates, and as such, must perform actions that will help them obtain tho...
Second Messenger Systems Involved in Reward and Addiction
With repeated psychostimulant administration, these are changes in dopaminergic and glutamatergic transmission in the nucleus accumbens. The figure depicts the major second messenger systems in the nucleus accumbens activated by dopamine and glutamate that are influenced by acute and/or repeated psychostimulant injections.
The findings suggest that therapeutics targeting the path between two critical brain regions, the amygdala and the nucleus accumbens, represent potential treatments for addiction and other neuropsychiatric diseases.
The results of behavioral experiments were given as mean ± SEM. A two-way ANOVA with repeated measures, followed by post hoc multiple pair-wise comparison Bonferroni test, was used to compare the 50% withdrawal threshold of PI versus control rats and SNI versus sham rats. For the FST, an unpaired two-tailed Students t test was used to compare the performances of PI versus control groups, CX546 versus DMSO groups, and CX546 versus saline groups. For dose-response experiments, a one-way ANOVA was used to compare the analgesia effects of CX546 with DMSO as control. For the experiment testing the duration of analgesic effects, a two-way ANOVA with repeated measures and post hoc multiple pair-wise comparison Bonferroni tests were used to compare mechanical hypersensitivity after CX546 versus DMSO (control) treatments. A two-way ANOVA with repeated measures, followed by post hoc multiple pair-wise comparison Bonferroni test, was also used to compare the 50% withdrawal threshold of CX546 versus ...
Our findings suggest opposing actions of Narp and NP1 versus NPR in cocaine-induced plasticity that parallel their differential actions in synaptogenesis and excitatory transmission. Narp and NP1 are able to multimerize and promote clustering of AMPAR (OBrien et al., 2002; Xu et al., 2003), whereas NPR is thought to bind to the Narp/NP1/AMPA clusters and promote internalization of the clustered receptors (Cho et al., 2008). Consistent with a shared AMPAR clustering function for Narp and NP1, deletion of either NP caused similar alterations in spontaneous and cocaine-induced behavior and desensitized the motor response elicited by stimulating AMPAR in the nucleus accumbens. Thus, although both Narp and NP1 deletion promoted cocaine-induced place preference, NPR deletion was without effect. Narp or NP1 deletion inhibited AMPA-induced locomotion, whereas NPR deletion potentiated the motor effect of AMPA. In addition, although Narp and NP1 KO showed reduced time in the center of a novel ...
We employed dual probe microdialysis in the nucleus accumbens and ipsilateral ventral pallidum of the halothane anaesthetized rat to investigate the effect of intra-accumbens perfusion with the sulphated octapeptide cholecystokinin (CCK-8S, 10-1000 nM, 60 min) alone and in the presence of the selective CCK1 and CCK2 receptor antagonists L-364,718 (10 and 100 nM) and PD134308 (10 nM), tetrodotoxin (TTX, 1000 nM) and the GABA(A) receptor antagonist bicuculline (1000 nM), on dialysate GABA levels in the ventral pallidum ...
A group of scientists from the University of Copenhagen has created a model that shows how some types of ADHD medicine influence the brains reward system. The model makes it possible to understand the effect of the medicine and perhaps in the longer term to improve the development of medicine and dose determination. The new research results have been published in the Journal of Neurophysiology
Alcohol, Vol. 27 (3), p. 193-198. ISSN 0741-8329. Article.. Peana, Alessandra Tiziana and Muggironi, Giulia and Fois, Giulia R. and Zinellu, Manuel and Vinci, Stefania and Acquas, Elio (2011) Effect of opioid receptor blockade on acetaldehyde self-administration and ERK phosphorylation in the rat nucleus accumbens. ...
Commonalities in addictive behavior, such as craving, stimuli-driven drug seeking, and a high propensity for relapse following abstinence, have pushed for a unified theory of addiction that encompasses most abused substances. This unitary theory has recently been challenged - citing distinctions in structural neural plasticity, biochemical signaling, and neural circuitry to argue that addiction to opioids and psychostimulants is behaviorally and neurobiologically distinct. Recent more selective examination of drug-induced plasticity has highlighted that these two drug classes promote an overall reward circuitry signaling overlap through modifying excitatory synapses in the nucleus accumbens - a key constituent of the reward system ...
High ratios of mu1 to mu2 binding were noted in frontal cortex, nucleus accumbens, rostral striatum, ventral pallidum, ventral periaqueductal gray matter, and laminae I and II of the spinal cord ...
This conflict model is used to measure the impairment of inhibitory control after exposure to addictive drugs, or other factors that...