Cocaine and Amphetamine Increase Extracellular Dopamine in the Nucleus Accumbens of Mice Lacking dopamine in the dorsal striatum. Here we report that, in DAT-KO mice, cocaine and amphetamine increase; cocaine; amphetamine; reboxetine Cocaine and amphetamine psychostimulants are abused by hu- mans (Johanson
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A growing body of evidence suggests that several protein kinases are involved in the expression of pharmacological actions induced by a psychostimulant methamphetamine. The present study was designed to investigate the role of the Rho/Rho-associated kinase (ROCK)-dependent pathway in the expression of the increase in extracellular levels of dopamine in the ...
PubMed
In vivo microdialysis combined with HPLC-EC analysis was used to monitor extracellular glutamate in the n. accumbens of Sprague-Dawley rats during footshock and food delivery. The footshock presentation resulted in a delayed increase in extracellular glutamate level, whereas the food intake caused its decrease. The ...
The effects of propofol, a hydrophobic intravenous anaesthetic, and fentanyl, an opiate analgesic, on extracellular concentrations of gamma-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied using in vivo brain microdialysis. The concentrations of GABA in the microdialysate of the nucleus accumbens reached a stable ...
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 ...
In vivo microdialysis combined with high-performance liquid chromatography and electrochemical detection was used to monitor extracellular glutamate levels in the medial nucleus accumbens of Sprague-Dawley rats during their feeding behaviour. Consumption of a palatable new diet or a diet to which rats were previously exposed caused a decrease in ...
Beta-endorphin is an endogenous opioid peptide that has been hypothesized to be involved in the behavioral effects of drugs of abuse including psychostimulants. Using microdialysis, we studied the effect of cocaine on extracellular levels of beta-endorphin in the nucleus accumbens, a brain region involved in the reinforcing effects of psychostimulant ...
Receptor-specific compounds were applied by retrograde microdialysis to the ventral tegmental area (VTA) of the rat brain. The effect of the intrategmental infusions on extracellular dopamine in the ipsilateral nucleus accumbens were recorded with a second microdialysis probe. Intrategmental infusion of muscimol (10-40 microM) or baclofen (50 microM) ...
By means of in vivo microdialysis combined with HPLC/EC analysis it was shown that presentation to a rat of an inedible object (a piece of rubber) or an aversive object (food of bitter taste) instead of expected food caused a marked increase in extracellular glutamate level in n. accumbens. In rats not expecting food reinforcement, ...
Experiments on Sprague-Dawley rats using vital intracerebral dialysis and HPLC with electrochemical detection demonstrated that presentation of the animals with inedible imitation food or food containing a bitter flavor instead of the expected food reinforcement led to rapid increases in glutamate levels in the intercellular space of the nucleus accumbens. ...
The influence of dopamine D1- and D2-like receptors blockage on glutamate level in the n. accumbens of Sprague-Dawly rats during feeding was investigated by in vivo microdialysis combined with HPLC-EC analysis. Food intake resulted in a decrease in extracellular glutamate level. Infusion of D1-like dopamine receptor-blocker (SCH-23390, 0.01 mM) into the n. ...
Modafinil (MOD) is a wakefulness-promoting drug that improves the alertness levels in narcolepsy; however, the molecular mechanism of action remains to be elucidated. We found that after a single icv injection of MOD (10 microg/5 microl) the extracellular levels of dopamine (DA) and l-DOPA collected from the nucleus accumbens were ...
By means of in vivo microdialysis combined with HPLC analysis, we have shown that extracellular glutamate level in the rat n. accumbens increases during a simultaneous presentation of a palatable diet and a tone previously paired with a footshock, the magnitude of the extracellular glutamate ...
Nucleus accumbens dopamine (DA) is a critical component of the brain circuitry regulating behavioral output during reinforcement-seeking behavior. Several studies have investigated the characteristics of accumbens DA release during the performance of well-learned operant behaviors, but relatively few have focused on the initial acquisition of particular ...
In the present study, we have characterized the neuropharmacological regulation of nicotine-induced increases in extracellular nucleus accumbens glutamate levels. Sprague-Dawley rats were stereotaxically implanted with 2 mm microdialysis probes in the nucleus accumbens and on the following day in vivo microdialysis ...
It has been proved that agmatine inhibits opioid dependence, yet the neural mechanism remains unclear. In the present study, the effect of agmatine on the neuroadaptation of glutamate neurotransmission induced by morphine dependence, including changes of the extracellular glutamate level and glutamate receptors in the nucleus accumbens was investigated. We ...
The effects of the delta2-opioid receptor agonist, deltorphin II, on extracellular levels of dopamine in the rat nucleus accumbens were investigated in awake animals by in vivo brain microdialysis. In agreement with previous studies, perfusion of deltorphin II (50.0 nmol) into the nucleus accumbens significantly ...
An opioid antagonist injected in the nucleus accumbens of a morphine-dependent rat will lower extracellular dopamine and release acetylcholine (ACh), as also seen in opiate withdrawal. It was hypothesized that raising extracellular ACh experimentally would be aversive as reflected by the induction of a conditioned taste aversion. Rats ...
, and Amphetamine M. Foster Olive,1 Heather N. Koenig,1 Michelle A. Nannini,1 and Clyde W. Hodge2 1Department (i.e., ethanol, cocaine, D-amphetamine, and nicotine) would increase neurotransmission of endogenous radioimmunoassay. Acute administration of ethanol, cocaine, and D-amphetamine transiently elevated extracellular
that are regulated by multiple mechanisms, including release, uptake, synthesis, and metabolism. In contrast, FSCV) Cocaine and amphetamine increase extracellular do- pamine in the nucleus accumbens of mice lacking and amphetamine in mice lacking the dopamine transporter. Nature 379:606�612. Grace AA (2000) The tonic
The dopamine reuptake inhibitor bupropion has clinically been proven to improve depression and treatment-resistant depression. We examined its influence on the duration of immobility during the forced swim test in adrenocorticotropic hormone (ACTH)-treated rats and further analyzed the possible role of dopamine receptors in this effect. Additionally, the mechanism by which bupropion acts in this ...
The inhibitory effects of 4-phenyl-1,2,3,4-tetrahydroisoquinoline (4-PTIQ) on methamphetamine-induced increases in dopamine and locomotion were investigated. Methamphetamine hydrochloride (10 micrograms) microinjected into the nucleus accumbens increased both locomotor activity and extracellular dopamine levels, ...
We compared amphetamine-induced dopamine release in the nucleus accumbens of vole species that exhibit differing mating systems to examine potential interactions between social organization and substance abuse. We found no species or regional differences in basal extracellular dopamine, however, monogamous voles had greater and longer-lasting ...
PubMed Central
The effects of clonidine, an alpha2 adrenoceptor agonist, on extracellular concentrations of dopamine and gamma-aminobutyric acid (GABA) in the nucleus accumbens of rats were studied by using in vivo brain microdialysis. Clonidine (5 microg/kg i.v.) significantly decreased the brain microdialysate concentration of dopamine in the nucleus ...
Increased caloric intake in dietary obesity could be driven by central mechanisms that regulate reward-seeking behavior. The mesolimbic dopamine system, and the nucleus accumbens in particular, underlies both food and drug reward. We investigated whether rat dietary obesity is linked to changes in dopaminergic neurotransmission in that region. ...
The effects of the mu-receptor agonist fentanyl on extracellular levels of dopamine in rat nucleus accumbens were studied in awake animals by in vivo brain microdialysis. Fentanyl dose-dependently increased the levels of dopamine when given intravenously (microg/kg) or via a microdialysis probe placed into the ventral tegmental area or ...
Conditions of increased cognitive or emotional demand activate dopamine release in a regionally selective manner. Whereas the brief millisecond response of dopamine neurons to salient stimuli suggests that dopamine�s influence on behaviour may be limited to signalling certain cues, the prolonged availability of dopamine in regions such as the prefrontal cortex and nucleus ...
The mu- and delta-opioid receptors located at the terminal level in nucleus accumbens are involved in the opiate modulation of dopamine release in this brain area. However, recent studies suggest that the effects of opioid drugs on the core subregion of nucleus accumbens may completely differ from those observed in the shell. We used in vivo microdialysis ...
Oxytocin regulates partner preference formation and alloparental behavior in the socially monogamous prairie vole (Microtus ochrogaster) by activating oxytocin receptors in the nucleus accumbens of females. Mating facilitates partner preference formation, and oxytocin-immunoreactive fibers in the nucleus accumbens have been described in prairie voles. ...
Activation of metabotropic glutamate receptors by injecting (S)3,5-dihydroxyphenylglycine (DHPG) in nucleus accumbens (NAcc) increases motor activity by different mechanisms in control rats and in rats with chronic liver failure due to portacaval shunt. In control rats DHPG increases extracellular dopamine in NAcc ...
In vivo microdialysis combined with a high-performance liquid chromatography was used to monitor extracellular glutamate (GLU) levels in the nucleus accumbens (N.Acc) of Sprague-Dawley rats during their behavioral responses to the concurrent presentation of appetitive and conditioned aversive stimuli. The presentation of a highly palatable diet followed by ...
Olanzapine, an atypical antipsychotic, has a broad receptor binding profile, which may account for its pharmacological effects in schizophrenia. In vitro receptor binding studies showed a high affinity for dopamine D2, D3, and D4 receptors; all 5-HT2 receptor subtypes and the 5-HT6 receptor; muscarinic receptors, especially the M1 subtype: and alpha 1-adrenergic receptors. In vivo studies showed ...
ContextModafinil, a wake-promoting drug used to treat narcolepsy, is increasingly being used as a cognitive enhancer. Although initially launched as distinct from stimulants that increase extracellular dopamine by targeting dopamine transporters, recent preclinical studies suggest otherwise.ObjectiveTo measure the acute effects of ...
The group III metabotropic glutamate receptor 7 (mGluR7) has been implicated in many neurological and psychiatric diseases, including drug addiction. However, it is unclear whether and how mGluR7 modulates nucleus accumbens (NAc) dopamine (DA), l-glutamate or ?-aminobutyric acid (GABA), important neurotransmitters believed to be ...
Adolescents differ from adults in their acute sensitivity to several drugs of abuse, but little is known about the long-term neurobehavioral effects of adolescent drug exposure. To explore this further, we evaluated the locomotor responses to repeated cocaine administration in adolescent and adult male DBA/2J mice and alterations in extracellular levels of dopamine (DA) and ...
In extracellular recordings from chloral hydrate anesthetized rats the 5-HT3 antagonist, BRL 46470A, failed to prevent or reverse the increase in dopamine cell firing rate produced by systemic or iontophoretically applied morphine. A second 5-HT3 antagonist, tropesitron, was similarly found to be ineffective in antagonizing the effects of systemic ...
In vivo microdialysis with HPLC-ED was used to measure dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens of the rat, prior, during, and after 15-min periods of electrical brain stimulation at sites in the ventral tegmental area (VTA) that supported intracranial self-stimulation ...
1. Extracellular 5-hydroxytryptamine (5-HT) was determined in dorsal raphe nucleus (DRN), median raphe nucleus (MRN) and nucleus accumbens by use of microdialysis in unanaesthetized rats. 2. Infusion of the gamma-aminobutyric acid (GABA)A receptor agonist muscimol into DRN and MRN resulted in decreased 5-HT in DRN and MRN, respectively. Muscimol infusion ...
Rats of the Lewis (LEW) strain show a greater preference for drugs of abuse than do Fisher 344 (F344) rats. The in vivo microdialysis procedure was used to examine basal and cocaine-evoked extracellular (EC) levels of dopamine (DA), DOPAC, and HVA in the nucleus accumbens (NAc) of F344 and LEW rats. The basal EC levels of the DA metabolites DOPAC and HVA ...
Energy Citations Database
The experimental question is whether hypothalamic opioids, known to stimulate consummatory behavior, control a link to the nucleus accumbens (NAc). It was hypothesized that opioids injected in the hypothalamic paraventricular nucleus (PVN) alter the balance of dopamine (DA) and acetylcholine (ACh) in the NAc in a manner that fosters appetite for food or ethanol. Rats were ...
Oxytocin (100�ng) injected unilaterally into the ventral subiculum of the hippocampus induces penile erection episodes, which started 30�min after treatment and were abolished by the prior injection of d(CH(2))(5)Tyr(Me)(2)-Orn(8)-vasotocin (2�?g), an oxytocin receptor antagonist, into the ventral subiculum. Oxytocin-induced penile erection occurred 15�min after the ...
In Sprague-Dawley rats in was shown by means of in vivo microdialysis combined with HPLC-EC analysis that the blockade of D2-dopamine receptors of the n. accumbens by raclopride (10 microM) completely prevents a decrease in accumbal extracellular glutamate level induced by food intake. PMID:11548610
The ability of estrogen to modulate mesolimbic dopamine (DA) was examined using in vivo voltammetry. Estrogen priming (5 micrograms, 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 ...
The activation of dopamine (DA) neurotransmission plays a crucial role in the behavioral responses to drugs of abuse. In particular, increased extracellular levels of DA within the mesolimbic pathway have been implicated in the rewarding and locomotor stimulatory properties of morphine. We investigated the behavioral responses to morphine in mice with a ...
The effects of caffeine on extracellular dopamine and acetylcholine have been studied in freely moving rats implanted with concentric microdialysis probes in the nucleus accumbens shell and core and in the medial prefrontal cortex. Intravenous administration of caffeine (0.25, 0.5, 1.0, 2.5 and 5.0 mg/kg) dose-dependently increased ...
Elevated dopamine levels are believed to contribute to the rewarding sensation of ethanol (EtOH), and previous research has shown that strychnine-sensitive glycine receptors in the nucleus accumbens (nAc) are involved in regulating dopamine release and in mediating the reinforcing effects of EtOH. Furthermore, the osmoregulator taurine, which is released from astrocytes ...
Relapse is one of the most problematic aspects in the treatment of alcoholism and is often triggered by alcohol-associated environmental cues. Evidence indicates that glutamate neurotransmission plays a critical role in cue-induced relapse-like behavior, as inhibition of glutamate neurotransmission can prevent reinstatement of alcohol-seeking behavior. However, few studies have examined specific ...
The metabotropic glutamate receptor 7 (mGluR7) has been reported to be involved in cocaine and alcohol self-administration. However, the role of mGluR7 in relapse to drug seeking is unknown. Using a rat relapse model, we found that systemic administration of AMN082, a selective mGluR7 allosteric agonist, dose-dependently inhibits cocaine-induced reinstatement of drug-seeking behavior. Intracranial ...
In the United States, one-third of infected individuals contracted Human Immunodeficiency Virus-1 (HIV-1) via injecting drugs with contaminated needles or through risky behaviors associated with drug use. Research demonstrates concomitant administration of psychostimulants and HIV-1-proteins damage neurons to a greater extent than viral proteins or the drug alone. To model the onset of ...
Dopamine transmission within the nucleus accumbens has been implicated in associative reinforcement learning. We investigated the effect of appetitive classical conditioning on dopamine efflux in the rat nucleus accumbens shell and core, as dopamine may be differentially activated by conditioned and unconditioned stimuli (CS, US) in these subregions. After ...
Recent advances suggest that acetaldehyde mediates some of the neurobiological properties of ethanol. In a recent study, we have shown that ethanol elicits the phosphorylation of extracellular signal-regulated kinase (pERK) in the nucleus accumbens and extended amygdala, via a dopamine D(1) receptor-mediated mechanism. The aim of this study was to ...
Acute administration of antipsychotic drugs increases dopamine (DA) neuron activity and DA release via D2 receptor blockade. However, it is unclear whether the DA neuron activation produced by antipsychotic drugs is due to feedback from postsynaptic blockade or is due to an action on DA neuron autoreceptors. This was evaluated using two drugs: the first-generation ...
Background and purpose: The designer drug 1-(4-methylphenyl)-2-methylaminopropan-1-one (4-methylmethcathinone, mephedrone) is reported to possess psychostimulant, entactogenic and hallucinogenic effects. The purpose of this study was to examine the effects of acute administration of mephedrone on extracellular levels of dopamine (DA) and serotonin (5-HT) in the nucleus ...
Selective serotonin reuptake inhibitors, such as fluoxetine, have demonstrated the ability to alleviate behavioral depression in the forced swim test; however, the sites and mechanisms of their actions remain to be further elucidated. Previous studies have suggested that behavioral depression in the swim test is mediated in part by acetylcholine (ACh) stimulating the cholinergic M1 receptors in ...
SYSTEMIC AND INTRA-ACCUMBENS ADMINISTRATION OF AMPHETAMINE DIFFERENTIALLY AFFECTS CORTICAL experiments tested the hypothesis that the amphetamine-induced increase in dopamine release in the nucleus amphetamine to stimulate cortical acetylcholine release. The effects of systemic or intra
Intra-Accumbens Amphetamine Increases the Conditioned Incentive Salience of Sucrose Reward. Berridge Department of Psychology, University of Michigan, Ann Arbor, Michigan 48109 Amphetamine bilateral micro- injection of intra-accumbens vehicle or amphetamine (0.0, 2.0, 10.0, or 20.0 g/0.5 l
Reexposure to cocaine-associated environments promotes relapse to cocaine seeking and represents a persistent impediment to successful abstinence. Neurobiological adaptations are thought to underlie the preservation of drug-seeking behavior during protracted withdrawal periods, possibly including changes associated specifically with cocaine-paired contexts. We measured GluR(1) (S845) and ...
In addition to dopamine (DA), evidence indicates that glutamatergic regulation of the mesolimbic reward pathway is involved in mediating the abuse-related effects of psychostimulants, including amphetamine. Since rats raised in an enrichment condition (EC) during development are more sensitive to the locomotor stimulant effects of acute amphetamine compared to rats raised in an impoverished ...
Dopaminergic systems are thought to play a major role in the stimulant and reinforcing properties of drugs of abuse, including ethanol. The present study describes the effects of local perfusion with ethanol (and other alcohols) on extracellular dopamine in the striatum and nucleus accumbens. Following the establishment of basal dopamine levels (2-3 h), ...
Dynamic changes in accumbens dopamine correlate with learning during intracranial self University of New Jersey, Piscataway, NJ, April 23, 2008 (received for review December 4, 2007) Dopamine in extracellular dopamine were measured during ICSS in the rat NAc shell with fast-scan cyclic voltammetry
Repeated administration of low doses of ethanol gradually increases locomotor responses to ethanol in adult Swiss mice. This phenomenon is known as behavioral sensitization. However, we have shown that adolescent Swiss mice show either behavioral tolerance or no sensitization after repeated ethanol injections. Although the mesolimbic dopamine system has been extensively ...
Infusion of muscimol (5 X 10[-5] M, 60 min) into the nucleus accumbens (NAC) through a dialysis membrane caused a significant increase in extracellular dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC). Fos-like immunoreactivity induced by intra-NAC infusion of muscimol was seen ipsilaterally in many accumbofugal ...
In recent microdialysis studies, increased extracellular concentrations of taurine after high ethanol dose administration were identified in various rat brain regions. The mechanisms by which ethanol caused these increases in extracellular taurine concentration remained unclear but could be related to ...
Cocaine (COC) inhibits the re-uptake of dopamine. However, the dopamine response to COC also depends on dopamine inside storage vesicles. The aim of this study was to investigate whether rats that differentially respond to COC differ in their dopaminergic storage capacity of the nucleus accumbens. Total and vesicular levels of accumbal dopamine as well as accumbal vesicular ...
Our previous studies have shown that local perfusion of morphine causes an increase of extracellular ascorbic acid (AA) levels in nucleus accumbens (NAc) of freely moving rats. Lines of evidence showed that glutamatergic and GABAergic were associated with morphine-induced effects on the neurotransmission of the brain, especially on the ...
We previously demonstrated that the discriminative stimulus effects of the ?-opioid receptor agonist U-50,488H were associated with its aversive effects in rats. However, its molecular signaling mechanisms are not fully understood. The aim of this study was to investigate the intracellular signaling that plays a role in mediating the discriminative stimulus effect induced by U-50,488H. To better ...
Abuse of psychoactive substances can lead to drug addiction. In animals, addiction is best modeled by drug self-administration paradigms. It has been proposed that the crucial common denominator for the development of drug addiction is the ability of drugs of abuse to increase extracellular concentrations of dopamine in the nucleus ...
In the rodent nucleus accumbens (NAc), cocaine elevates levels of brain-derived neurotrophic factor (BDNF). Conversely, BDNF can augment cocaine-related behavioral responses. The latter could reflect enhancement of ?-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) transmission, because AMPARs in the NAc mediate some cocaine-induced behaviors. Furthermore, ...
Dopaminergic activity in the mesocorticolimbic system is associated with reinforcing properties of psychostimulant drugs. We previously demonstrated that increased gamma-aminobutyric acid (GABA)-ergic activity produced by gamma-vinyl GABA [D,L-4-amino-hex-5-enoic acid (Vigabatrin(R))], an irreversible inhibitor of GABA-transaminase, attenuated cocaine, nicotine, heroin, ...
Many drugs of abuse exert their addictive effects by increasing extracellular dopamine in the nucleus accumbens, where they likely alter the plasticity of corticostriatal glutamatergic transmission. This mechanism implies key molecular alterations in neurons in which both dopamine and glutamate inputs are activated. ...
Several studies on the differences between ethanol-preferring versus non-preferring rat lines suggest an innate deficit in the mesolimbic dopaminergic system as an underlying factor for ethanol volition. Rats would try to overcome such deficit by engaging in a drug-seeking behaviour, when available, to drink an ethanol solution over water. Thus, in the present study we compared the effect of a ...
It has been reported that in the medial nucleus accumbens (NAc) there are nerve terminals which contain either the neuropeptide cholecystokinin (CCK) or the catecholamine dopamine (DA), as well as terminals which contain both. In this study, the authors have examined the action of CCK-peptides on the basal and potassium-evoked release of (TH)DA within this structure. The in ...
The effect of interactions among mu- and delta-opioid receptors, especially the putative delta(1)- and delta(2)-opioid receptors, in the nucleus accumbens on accumbal dopamine release was investigated in awake rats by in vivo brain microdialysis. In agreement with previous studies, perfusion of the nucleus accumbens with the mu-, delta(1)- and ...
Evidence suggests that elevations in extracellular serotonin (5-HT) in the brain can diminish stimulant effects of dopamine (DA). To assess this proposal, we evaluated the pharmacology of amphetamine analogs (m-fluoroamphetamine, p-fluoroamphetamine, m-methylamphetamine, p-methylamphetamine), which display similar in vitro potency as DA releasers (EC(50) = 24-52 nM) but differ ...
Associations between drugs of abuse and cues facilitate the acquisition and maintenance of addictive behaviors. Although significant research has been done to elucidate the role that simple discriminative or discrete conditioned stimuli (e.g., a tone or a light) play in addiction, less is known about complex environmental cues. The purpose of the present study was to examine the role of a musical ...
Chronic cocaine increases neurotensin gene expression in the shell of the nucleus accumbens. Abstract The effects of chronic cocaine administration on neurotensin (NT) mRNA expression were investigated in the rat brain using in situ hybridization. Adult Wistar rats were injected daily with cocaine
1. The effect of single and repeated (once daily for 23 days) oral doses of 20 and 60 mg kg-1 clozapine on dopamine release and metabolism were studied by intracerebral dialysis in the striatum and nucleus accumbens of conscious rats. 2. The basal output of dopamine, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum and nucleus ...
A key in understanding the neurobiology of addiction and developing effective pharmacotherapies is revealing drug-induced plasticity that results in heightened relapse susceptibility. Previous studies have demonstrated that increased extracellular glutamate, but not dopamine, in the nucleus accumbens core (NAcc) is necessary for ...
We have previously demonstrated that glycine receptors in the nucleus accumbens (nAc) are involved in modulating both basal and ethanol-induced dopamine output in the same brain region. Ethanol is known to induce a release of both taurine and dopamine in the nAc, but the relationship between these two neuromodulators has not been investigated thoroughly. In vivo microdialysis ...
Environment-induced relapse is a major concern in drug addiction because of the strong associations formed between drug reward and environment. Cocaine-conditioned place preference is an ideal experimental tool to examine adaptations in the molecular pathways that are activated upon re-exposure to an environment previously paired with drug reward. To better understand the mechanism of ...
Changes in ?-amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) surface expression in the rodent nucleus accumbens (NAc) are produced by cocaine exposure and implicated in addiction-related behaviors. The direction of change depends on the animal's prior drug history. However, little is known about the effect of a single exposure to cocaine on AMPAR distribution ...
Impaired glutamate homeostasis in the nucleus accumbens has been linked to cocaine relapse in animal models, and results in part from cocaine-induced downregulation of the cystine-glutamate exchanger. In addition to regulating extracellular glutamate, the uptake of cystine by the exchanger is a rate-limiting step in the synthesis of glutathione (GSH). GSH ...
The present studies were conducted to investigate the relationship between discriminative stimulus effects of indirectly acting monoaminergic psychostimulants and their ability to increase extracellular levels of dopamine (DA) in the nucleus accumbens (NAcb) shell. First, the behavioral effects of methamphetamine (MA), cocaine (COC), ...
Developmental exposure to polychlorinated biphenyls (PCBs) induces motor alterations in humans by unknown mechanisms. It remains unclear whether: (a) all non-dioxin-like (NDL) PCBs are neurotoxic or it depends on the grade of chlorination; (b) they have different neurotoxicity mechanisms; (c) they affect differently males and females. The aims of this work were to assess: (1) whether perinatal ...
Extracellular single-unit recordings and iontophoresis were used to examine the effects of different selective sigma receptor ligands on dopaminergic and glutamatergic N-methyl-D-aspartate (NMDA) neurotransmissions both in origin (A10 and A9 areas) and terminal (nucleus accumbens and caudate nucleus) regions of the rat mesolimbic and nigrostriatal ...
Glutamatergic signaling plays an important role in the behavioral and molecular plasticity observed in behavioral sensitization to cocaine. Redistribution of the glutamate receptors in the synaptosomal membrane fraction was investigated in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area at 1 or 21 days of withdrawal in behaviorally sensitized rats. At ...
BACKGROUND: Repeated exposure to drugs of abuse and stress increase dynorphin, a ? opioid receptor (KOR) ligand, in the nucleus accumbens (NAc). Acute KOR activation produces dysphoria that might contribute to addictive behavior. How repeated KOR activation modulates reward circuitry is not understood. METHODS: We used intracranial self-stimulation (ICSS), ...
REVIEW Linking nucleus accumbens dopamine and blood oxygenation Brian Knutson & Sasha E. B. Gibbs-Verlag 2007 Abstract Rationale Animal research suggests that anticipation of reward can elicit dopamine in the NAcc. However, the physiolog- ical relationship between dopamine release and BOLD signal increases
between the effects of intra-accumbens administration of amphetamine and exposure to a novel environment Previous research has demonstrated an interaction between the effects of amphetamine and exposure, the administration of intra-accumbens amphetamine was hypothesized to potentiate the increase in cortical
The knowledge of feeding behavior mechanisms gained through brain microdialysis is reviewed. Most of the chemical changes so far reported concern to the limbic system in rodents. A picture showing increases and decreases of extracellular neurotransmitters correlating to different aspects of feeding behavior is gradually emerging. Depending on the region, ...
BackgroundThe nucleus accumbens (NAc) has been implicated in the neurochemical effects of ethanol (EtOH). Evidence suggests that repeated EtOH exposures and chronic EtOH drinking increase dopamine (DA) neurotransmission in the NAc due, in part, to a reduction in D2 autoreceptor function. The objectives of the current study were to ...
In vivo brain microdialysis was used to investigate the influence of lobeline on dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) overflow in the core of the nucleus accumbens of freely-moving rats pretreated with nicotine (0.4 mg x kg(-1), s.c., once per day for 5 days). Locomotion was also recorded. Lobeline, at doses of 0.7, 4.0 and 10.0 mg x kg(-1), i.p., failed to ...
In vivo brain microdialysis was used to investigate the influence of lobeline on dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) overflow in the core of the nucleus accumbens of freely-moving rats pretreated with nicotine (0.4?mg?kg?1, s.c., once per day for 5 days). Locomotion was also recorded.Lobeline, at doses of 0.7, 4.0 and ...
Orexin (ORX) plays a critical role in reward-seeking behavior for natural rewards and drugs of abuse. The mesolimbic dopamine (DA) pathway that projects into the nucleus accumbens (NAc) from the ventral tegmental area is deeply involved in the neural mechanisms underlying reward, drug abuse and motivation. A recent study demonstrated that ORX-immunopositive fibers densely ...
Gabapentin is a ?-aminobutyric acid (GABA) analogue, with GABAmimetic pharmacological properties. Gabapentin is used for the treatment of seizures, anxiety and neuropathic pain. It has been proposed that gabapentin may be useful in the treatment of cocaine dependence. However, clinical trials with gabapentin have shown conflicting results, while preclinical studies are sparse. In the present ...
A growing body of evidence indicates that enhanced AMPA-mediated glutamate transmission in the core of the nucleus accumbens is critically involved in cocaine priming-induced reinstatement of drug seeking, an animal model of relapse. However, the extent to which increased glutamate transmission in the other major subregion of the nucleus ...
It is well known that the nucleus accumbens plays an important role in drug reinforcing effect and relapse. However, the cellular neuroadaptations that take place in accumbens neurons after repeated drug exposure are still not well understood, especially for opioids. Here, we examined how nucleus accumbens neuronal excitability becomes ...
Previous studies have shown that the dopamine (DA) uptake blocker methylphenidate, a psychostimulant widely used for the treatment of attention-deficit hyperactivity disorder (ADHD), prevents the neurotoxic effects of the highly abused DA releaser methamphetamine. However, there is a lack of information about the pharmacological interactions of these two drugs at the behavioral level. When ...
Like many psychostimulant drugs, nicotine elevates extracellular and synaptic dopamine (DA) concentrations in the nucleus accumbens (NAc). This elevation has been linked to its reinforcing properties. Dopaminergic transmission within the NAc is modulated by gamma-aminobutyric acid (GABA). Therefore, we examined the utility of gamma vinyl-GABA (GVG, ...
The nucleus accumbens is critical for reward-guided learning and decision-making. It is thought to "gate" the flow of a diverse range of information (e.g., rewarding, aversive, and novel events) from limbic afferents to basal ganglia outputs. Gating and information encoding may be achieved via cross-frequency coupling, in which bursts of high-frequency activity occur ...
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Apathy refers to a reduction in self-initiated behavior, and it is commonly reported by patients infected with human immunodeficiency virus (HIV). It remains unclear whether apathy among HIV patients reflects a direct effect of the virus on subcortical brain circuits or a secondary neuropsychiatric symptom. In the present study we examined the relationship between ratings of apathy and ...
Muscarinic acetylcholine receptors in the nucleus accumbens play an important role in mediating the reinforcing effects of cocaine. However, there is a paucity of data regarding the role of accumbal muscarinic acetylcholine receptors in the reinstatement of cocaine-seeking behavior. The goal of these experiments was to assess the role of muscarinic acetylcholine receptors in ...
Until recently, the exact location of the avian nucleus accumbens within the basal forebrain had not been well established (Reiner et al. [2004] J Comp Neurol 473:377-414). While a number of previous studies have shown afferents and efferents of the presumptive "nucleus accumbens," detailed and accurate connection patterns of this newly recognized area are ...
We have previously shown, using radioligand binding studies, that N-methyl-d-aspartate (NMDA) NR1 and NR2A receptor subunits density was decreased in the forebrain of morphine-dependent rats. We have now determined if morphine-dependent rats display regional differences in NMDA receptor expression and whether such changes are functionally relevant. In morphine-dependent rats, the expression of NR1 ...
AMPA receptor (AMPAR) plasticity at glutamatergic synapses in the mesoaccumbal dopaminergic pathway has been implicated in persistent cocaine-induced behavioral responses; however, the precise mechanism underlying these changes remains unknown. Utilizing cocaine psychomotor sensitization, we have examined phosphorylation of GluA1 at key residues serine 845 (S845) and S831, as well as GluA1 cell ...
The mesoaccumbens dopamine system is intricately in-volved in the locomotor stimulation produced by cocaine and sensitization of this effect following repeated cocaine administration. The mechanisms responsible for the ex-pression of sensitized locomotion appear to involve alter-ations in both presynaptic (increased dopamine release) and postsynaptic ...
Studies have indicated that the metabotropic glutamate receptor 5 (mGluR5) antagonist 6-methyl-2-(phenylethynyl)-pyridine (MPEP) decreases ethanol self-administration, and the same receptor type was also suggested to be involved in the mechanism of action of the anti-craving substance acamprosate. Our previous research suggested that glycine receptors (GlyRs) in the nucleus ...
In the striatum, dopamine and acetylcholine (ACh) modulate dopamine release by acting, respectively, on dopamine D(2) autoreceptors and nicotinic ACh (nACh) heteroreceptors localized on dopaminergic nerve terminals. The possibility that functional interactions exist between striatal D(2) autoreceptors and nACh receptors was studied with in vivo microdialysis in freely moving rats. Local perfusion ...
Successful treatment of drug addiction is hampered by high relapse rates during periods of abstinence. Neuroadaptation in the medial prefrontal cortex (mPFC) is thought to have a crucial role in vulnerability to relapse to drug seeking, but the molecular and cellular mechanisms remain largely unknown. To identify protein changes that contribute to relapse susceptibility, we investigated synaptic ...
We report a reliable 5-min on-line monitoring of dopamine released from the dorsal striatum and the nucleus accumbens of rats using in vivo brain microdialysis. The detection limit for dopamine was approximately 20 fg in a 10-microl injection sample using high-performance liquid chromatography with electrochemical detection set-up. Basal levels of dopamine in the dorsal ...
The present study compares the extrapyramidal and neurochemical effects of clozapine and risperidone in rat caudate (corpus striatum) and nucleus accumbens (ventral striatum) dose-dependently. Animals injected with clozapine (2.5, 5.0 and 10.0 mg/kg IP) or risperidone (1.0, 2.5 and 5.0 mg/kg IP) in acute were sacrificed 1 h later to collect brain samples. Extrapyramidal side ...
Previously, we showed that NMDA antagonists enhance high-frequency oscillations (130-180?Hz) in the nucleus accumbens. However, whether NMDA antagonists can enhance high-frequency oscillations in other brain regions remains unclear. Here, we used monopolar, bipolar and inverse current source density techniques to examine oscillatory activity in the hippocampus, a region known ...
Pharmacological activation of group II metabotropic glutamate receptors (mGluR2/3) inhibits cocaine self-administration and reinstatement of drug-seeking behavior, suggesting a possible use of mGluR2/3 agonists in the treatment of cocaine dependence. In the present study, we investigated whether elevation of the endogenous mGluR2/3 ligand N-acetyl-aspartatylglutamate (NAAG) levels with the ...
In this review, we examine how experiences in social confrontations alter gene expression in mesocorticolimbic cells. The focus is on the target of attack and threat due to the prominent role of social defeat stress in the study of coping mechanisms and victimization. The initial operational definition of the socially defeated mouse by Ginsburg and Allee (1942) enabled the characterization of key ...
In Na(+) appetite neurobiology, it is essential to investigate whether endogenous opioids modulate the output of the neural substrates that are involved in both the detection and integration of Na(+) deficiency and the motivational aspect of Na(+) intake. Thus, evaluating the recruitment dynamics of enkephalin (ENK)-containing and/or mu-opioid receptor (?-OR)-expressing neurons in close ...
Brain norepinephrine and dopamine regulate a variety of critical behaviors such as stress, learning, memory, and drug addiction. Here, we demonstrate differences in the regulation of in vivo neurotransmission for dopamine in the anterior nucleus accumbens (NAc) and norepinephrine in the ventral bed nucleus of the stria terminalis (vBNST) of the anesthetized rat. Release of the ...
The impact of serotonergic neurotransmission on brain dopaminergic pathways has substantial relevance to many neuropsychiatric disorders. A particularly prominent role has been ascribed to the inhibitory effects of serotonin 2C receptor (5-HT2CR) activation on physiology and behavior mediated by the mesolimbic dopaminergic pathway, particularly in the terminal region of the ...
J. Neurochem. (2011) 118, 806-815. ABSTRACT: The cytochrome P450-mediated synthesis of dopamine from tyramine has been shown in vitro. The aim of the present study was to demonstrate the ability of rat cytochrome P450 (CYP) 2D to synthesize dopamine from tyramine in the brain in vivo. We employed two experimental models using reserpinized rats with a blockade of the classical pathway of dopamine ...
Glial cell line-derived neurotrophic factor (GDNF) activity in ventral tegmental area (VTA) mediates the time-dependent increases in cue-induced cocaine-seeking after withdrawal (incubation of cocaine craving). Here, we studied the generality of these findings to incubation of heroin craving. Rats were trained to self-administer heroin for 10 days (6 hours/day; 0.075 ...
During abstinence, memories of drug-associated cues persist for many months, and exposure to these cues often provokes relapse to drug use. The mechanisms underlying the maintenance of these memories are unknown. A constitutively active atypical protein kinase C (PKC) isozyme, protein kinase M ? (PKM?), is required for maintenance of spatial memory, conditioned taste aversion, and other memory ...
Relapse to cocaine-seeking behavior depends on increased glutamate transmission in key regions of the mesocorticolimbic motive circuit, including prefrontal cortex (PFC) and nucleus accumbens (NAcc). Because GLT1 is responsible for the uptake of ?90% of extracellular glutamate, we tested the hypothesis that ...
The nucleus accumbens (NAc) has emerged as an important part of the neural circuitry regulating depressive-like behaviors. Given that the NAc GABAergic medium spiny neurons project to the ventral pallidum (VP), it is reasonable to suggest that the VP may also be involved in these behaviors. Consequently, we explored the role of the VP GABAergic terminals during depressive-like ...
Background and purpose:In the present study we investigated, in a range of in vivo tests whether the antidepressant bupropion, and its metabolites shared the dopamine releasing effect of the chemically related dexamphetamine.Experimental approach:We compared bupropion and dexamphetamine in different neurochemical (microdialysis, DOPAC and HVA contents) and behavioural tests, assessing their ...
Alpha-methyl-p-tyrosine (AMPT) is known to inhibit the formation of dopamine (DA) in the cytosol of dopaminergic neurons and is therefore used to study the role of the cytosolic DA pools. AMPT is usually administered systemically. In the present study, however, the effects of locally infused AMPT on the efflux of DA from the nucleus accumbens and dorsal striatum were analyzed, ...
We studied the metabolic responses to different DA concentrations elicited by four doses of D-amphetamine (AMPH, 0, 0.25, 0.5, 1.0, or 3.0 mg/kg). We compared the degree of DA release (via microdialysis) with striatal cAMP activity and whole brain maps of cerebral blood volume (rCBV) changes (via pharmacological MRI, phMRI). Results: AMPH increased DA release in the ...
The superior efficacy of atypical vs. classical antipsychotic drugs to treat negative symptoms and cognitive deficits in schizophrenia appears related to their ability to enhance mesocortical dopamine (DA) function. Given that noradrenergic (NE) transmission contributes to cortical DA output, we assessed the ability of NE-targeting drugs to modulate DA release in medial prefrontal cortex (mPFC) ...
?-1 Receptors are endoplasmic reticulum (ER) chaperones that are implicated in the neuroplasticity associated with psychostimulant abuse. We immunocytochemically examined the distribution of ?-1 receptors in the brain of drug-naive rats and then examined the dynamics of ?-1 receptors and other ER chaperones in specific brain subregions of rats that self-administered methamphetamine, received ...
Pharmacologic MRI (phMRI) uses functional MRI techniques to provide a noninvasive in vivo measurement of the hemodynamic effects of drugs. The cerebral blood volume change (?CBV) serves as a surrogate for neuronal activity via neurovascular coupling mechanisms. By assessing the location and time course of brain activity in mouse mutant studies, phMRI can provide valuable insights into how ...
The mechanisms by which liver failure alters motor function remain unclear. It has been suggested that liver disease alters the neuronal circuit between basal ganglia and cortex that modulates motor function. Activation of group I metabotropic glutamate receptors in the nucleus accumbens (NAcc) by injecting (S)-3,5-dihydroxyphenylglycine (DHPG) activates this circuit and ...
Corticotropin-releasing factor (CRF) is a potent neuromodulator of stress-related behaviour but the neural mechanisms underlying these effects are not clear. Studies were designed to test the hypothesis that CRF-induced behavioural arousal involves interactions with brainstem serotonergic systems. To examine interactions between CRF and serotonergic systems in the regulation of behaviour, CRF (1 ...
BackgroundOleoylethanolamide (OEA) and palmitoylethanolamide (PEA) are amides of fatty acids and ethanolamine named N-acylethanolamines or acylethanolamides. The hydrolysis of OEA and PEA is catalyzed by the fatty acid amide hydrolase (FAAH). A number of FAAH inhibitors that increase the levels of OEA and PEA in the brain have been developed, including URB597. In the present ...
?-Opioid receptor stimulation attenuates psychostimulant-induced increases in extracellular dopamine in the caudate-putamen (CPu) and nucleus accumbens of adult rats, while reducing cocaine-induced locomotor activity and stereotyped behaviors. Because ?-opioid receptor agonists (e.g., U50,488 or U69,593) often affect the behavior of ...
In postmortem samples of caudate nucleus and nucleus accumbens from 48 schizophrenic patients, there were significant increases in both the maximum number of binding sites (Bmax) and the apparent dissociation constant (KD) for tritiated spiperone. The increase in apparent KD probably reflects the presence of residual neuroleptic drugs, ...
It has been known that monkeys will repeatedly press a bar for electrical stimulation in several different brain structures. We explored the possibility of using electrical stimulation in one such structure, the nucleus accumbens, as a substitute for liquid reward in animals performing a complex task, namely visual search. The animals had full access to water in the cage at ...
Exposure to drug-paired cues can trigger addicts to relapse into drug seeking. Although the molecular mechanisms underlying cue-elicited cocaine seeking are incompletely understood, the protein kinase extracellular signal�regulated kinase (ERK) is known to play an important role. Psychostimulants and their associated cues can activate ERK in medium spiny neurons of the ...
Tonic dopamine (DA) signaling is widely regarded as playing a central role in effort-based decision making and in the motivational control of instrumental performance. The current study used microdialysis to monitor changes in extracellular DA levels across subregions of the nucleus accumbens and dorsal striatum of rats as they lever pressed for food ...
Tonic dopamine (DA) signaling is widely regarded as playing a central role in effort-based decision-making and in the motivational control of instrumental performance. The current study used microdialysis to monitor changes in extracellular DA levels across subregions of the nucleus accumbens and dorsal striatum of rats as they lever pressed for food ...
RationaleRepeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high ...
Midbrain dopamine (DA) neurons in the substantia nigra pars compacta (SNc) and ventral tegmental area (VTA) exhibit somatodendritic release of DA. Previous studies indicate a difference between the Ca2+ dependence of somatodendritic DA release in the SNc and that of axonal DA release in dorsal striatum. Here, we evaluated the Ca2+ dependence of DA ...
Evolution of extracellular enzyme activities during manure composting S.M. Tiquia Environmental to determine the extracellular enzyme pro�les during composting, relate the activities of these enzymes manure composting. Results showed an overall increase in diversity and relative abundance of enzymes
Behavioral sensitization is an animal model for aspects of cocaine addiction. Cocaine-sensitized rats exhibit increased AMPA receptor (AMPAR) surface expression in the nucleus accumbens (NAc) which may in turn enhance drug seeking. To identify signaling pathways contributing to AMPAR up-regulation, we measured AMPAR surface expression and signaling pathway ...
Cocaine produces a motor-stimulant response in part by its actions within the mesolimbic dopamine system. Repeated exposure to cocaine induces an augmented motor activity response which is termed behavioral sensitization, or reverse tolerance. Previous studies have suggested that sensitization may result from increased dopamine neuronal activity in the A10 region; the origin ...
RationaleActivation of metabotropic glutamate (mGlu) 2/3 receptors may provide a novel strategy for treating schizophrenia. This effect is thought to be mediated through dopamine-independent mechanisms because mGlu2/3-receptor agonists have no considerable affinity for dopamine receptors. These agonists, however, reduce amphetamine-induced hyperlocomotion suggesting that they influence dopamine ...
Modafinil is prescribed for numerous medical conditions, but the drug's mechanism of action is unclear. Here, we examined the interaction of modafinil with receptors and transporters in vitro and compared pharmacological effects of the drug with those produced by indirect dopamine (DA) agonists 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR12909) and (+)-methamphetamine ...
Modafinil is prescribed for numerous medical conditions, but the drug's mechanism of action is unclear. Here, we examined the interaction of modafinil with receptors and transporters in vitro and compared pharmacological effects of the drug with those produced by indirect dopamine (DA) agonists 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR12909) and ...
Extensive pharmacological studies have recently emerged indicating that group 2 metabotropic glutamate receptors (mGluRs) comprising mGluR2 and mGluR3 subtypes are associated with several neurological and psychiatric disorders. mGluR2 is widely distributed both presynaptically and postsynaptically in a variety of neuronal cells, but the physiological role of mGluR2 in brain function is poorly ...
Aberrant dopamine-mediated behaviours are a hallmark of a number of psychiatric disorders, including substance use disorders and schizophrenia. It has been demonstrated recently that rodent models of these diseases display enhanced dopamine neuron activity throughout the ventral tegmental area (VTA). It is known, however, that the VTA is not a homogeneous structure, and that the dopamine neuron ...
3,4-methylenedioxymethamphetamine (MDMA) is a popular methamphetamine derivative associated with young adults and all-night dance parties. However, the enduring effects of MDMA at voluntary intake levels have not been extensively investigated. In this study, MDMA-influenced behaviors and core temperatures were assessed over the course of 20 daily MDMA self-administration sessions in rats. In vivo ...
3,4-Methylenedioxymethamphetamine (MDMA) is an amphetamine derivative and a popular drug of abuse that exhibits mild hallucinogenic and rewarding properties and engenders feelings of connectedness and openness. The unique psychopharmacological profile of this drug of abuse most likely is derived from the property of MDMA to promote the release of dopamine and serotonin (5-HT) in multiple brain ...
To study how hippocampal output signals conveying spatial and other contextual information might be integrated in the nucleus accumbens, tonically active accumbens neurons were recorded in three unrestrained rats as they performed spatial orientation tasks on an elevated round rotatable platform with four identical reward boxes symmetrically placed around ...
In order to investigate the relationship between dopamine transmission in the nucleus accumbens and operant behavior in mice, mice with 6-hydroxydopamine (6-OHDA)-induced dopamine depletion in the nucleus accumbens were tested for their performance in lever pressing tasks under FR schedules with 8 ratios from FR5 to FR120. The mice were given one 20-mg ...
There are numerous problems with the hypothesis that brain dopamine (DA) systems, particularly in the nucleus accumbens, directly mediate the rewarding or primary motivational characteristics of natural stimuli such as food. Research and theory related to the functions of mesolimbic DA are undergoing a substantial conceptual restructuring, with the traditional emphasis on ...
Nicotinic acetylcholine receptors (nAChRs) of ?4?2 and ?7 subtypes expressed in the brain neurons are involved in regulating memory and cognition. Their level is decreased upon several neurodegenerative disorders including Alzheimer's disease (AD), although the reasons for such a decrease are not completely understood. To test whether the nAChR-specific antibodies can affect the brain nAChRs and ...
There is growing evidence that propofol acts on affective and reward processes. We designed this study to assess the effect of propofol on the concentration of dopamine in the nucleus accumbens, a main component of the mesolimbic system. The concentration of dopamine in the nucleus accumbens was assessed by using in vivo brain microdialysis in freely ...
Previously, it was shown that ethanol-dependent animals display increased sensitivity to the general opioid receptor antagonist nalmefene compared to naltrexone. It was hypothesized that the dissociable effects of the two antagonists were attributable to a ?-opioid receptor mechanism. Nucleus accumbens dynorphin is upregulated following chronic ethanol ...
It has recently been established that the extracellular matrix is required for normal functional differentiation of mammary epithelia not only in culture, but also in vivo. The mechanisms by which extracellular matrix affects differentiation, as well as the nature of extracellular matrix constituents which have major impacts on mammary ...
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Combined activation of dopamine D1- and NMDA-glutamate receptors in the nucleus accumbens has been strongly implicated in instrumental learning, the process in which an individual learns that a specific action has a wanted outcome. To assess dopaminergic activity, we presented rats with two sessions (30 trials each) of a one-lever appetitive instrumental task and ...
Persistent symptoms of depression suggest the involvement of stable molecular adaptations in brain, which may be reflected at the level of chromatin remodeling. We find that chronic social defeat stress in mice causes a transient decrease, followed by a persistent increase, in levels of acetylated histone H3 in the nucleus accumbens, an important limbic ...
Several recent studies suggest functional and molecular interactions between striatal adenosine A(2A) and cannabinoid CB(1) receptors. Here, we demonstrate that A(2A) receptors selectively modulate reinforcing effects of cannabinoids. We studied effects of A(2A) receptor blockade on the reinforcing effects of delta-9-tetrahydrocannabinol (THC) and the endogenous CB(1) receptor ligand anandamide ...
The serotonergic system appears crucial for (�)-3,4-methylenedioxymethamphetamine (MDMA) reinforcing properties. Current evidence indicates that serotonin 5-HT2A receptors (5-HT2ARs) modulate mesolimbic dopamine (DA) activity and several behavioural responses related to the addictive properties of psychostimulants. This study evaluated the role of 5-HT2ARs in MDMA-induced reinforcement and ...
The finding that many drugs that have abuse potential and other natural stimuli such as food or sexual activity cause similar chemical changes in the brain, an increase in extracellular dopamine (DA) in the shell of the nucleus accumbens (NAccS), indicated some time ago that the reward mechanism is at least very similar for all stimuli ...
Previous examinations demonstrated periodic increases in striatal extracellular dopamine levels during dystonic attacks and changes in dopamine D1 and D2 receptor binding in the dt(sz) mutant hamster, an animal model of paroxysmal non-kinesiogenic dyskinesia in which dystonic episodes can be induced by stress. Since dopamine D3 receptors are involved in ...
A major goal of research on addiction is to identify the molecular mechanisms of long-lasting behavioural alterations induced by drugs of abuse. Cocaine and delta-9-tetrahydrocannabinol (THC) activate extracellular signal-regulated kinase (ERK) in the striatum and blockade of the ERK pathway prevents establishment of conditioned place preference to these drugs. However, it is ...
Nicotine self-administration (SA) is maintained by several variables, including the reinforcing properties of nicotine-paired cues and the nicotine-induced amplification of those cue properties. The nucleus accumbens (NAc) is implicated in mediating the influence of these variables, though the underlying neurophysiological mechanisms are not yet understood. In the present ...
Slow-onset, long-lasting dopamine reuptake blockers with reduced abuse potential have been suggested as maintenance therapies for cocaine addiction. We have synthesized a series of 3-(3',4'-dichlorophenyl)-1-indanamine monoamine reuptake inhibitors as candidates for such maintenance pharmacotherapy. The initial lead compound, the N,N-dimethyl analogue 30,640 was then subjected to testing in ...
Accumbal glycine modulates basal and ethanol-induced dopamine levels in the nucleus accumbens (nAc) as well as voluntary ethanol consumption. Also, systemic administration of the glycine transporter-1 inhibitor Org25935 elevates dopamine levels in nAc, prevents a further ethanol-induced dopamine elevation and robustly and dose-dependently decreases ethanol consumption in rats. ...
Sigma1 receptors (?1Rs) represent a structurally unique class of intracellular proteins that function as chaperones. ?1Rs translocate from the mitochondria-associated membrane to the cell nucleus or cell membrane, and through protein-protein interactions influence several targets, including ion channels, G-protein-coupled ...
Nucleus accumbens dopamine (DA) is a critical component of the brain circuitry regulating work output in reinforcement-seeking behavior and effort-related choice behavior. Moreover, there is evidence of an interaction between DA D(2) and adenosine A(2A) receptor function. Systemic administration of adenosine A(2A) antagonists reverses the effects of D(2) antagonists on tasks ...
An increasing body of evidence suggests that the nucleus accumbens (NAcc) is engaged in both incentive reward processes and in adaptive responses to conditioned and unconditioned aversive stimuli. Yet, it has been argued that NAcc activation to aversive stimuli may be a consequence of the rewarding effects of their termination, i.e., relief. To address ...
Glutamate Transmission in the Nucleus Accumbens Mediates Relapse in Cocaine Addiction Jennifer L Carolina, Charleston, South Carolina 29425 Elevated dopamine transmission in the nucleus accumbens in the nucleus accumbens, is a primary mediator of cocaine- induced reinstatement of drug-seeking behavior
The cytokine, interleukin-1? (IL1?) is a sleep regulatory substance whose expression is enhanced in response to neuronal stimulation. In this study, IL1? mRNA and immunoreactivity (IR) are evaluated after acute cocaine. First, IL1? mRNA levels were measured at the start or end of the light period after saline or acute exposure to a low dose of cocaine (5 mg/kg, intraperitoneal (ip)). IL1? mRNA ...
... GLU projections from the neo- or allocortex have been found to terminate in nucleus accumbens and other forebrain and hypothalamic nuclei. ...
DTIC Science & Technology
Substantia nigra dopamine neuronal activity in the primate is thought to be related to the error in predicting reward delivery. Dopamine release in rat nucleus accumbens has been shown to increase in relation to drug/food-seeking behaviour. It is not known how the release of dopamine in the striatum corresponds to the many distinct steps of a rewarded, ...
... fresh look at an invasive species, Didymosphenia geminata: Chemical and structural analysis of the extracellular polymers Increase in nuisance blooms ... ...
NBII National Biological Information Infrastructure
1. The effects of the glycine/NMDA receptor antagonist, (+)-HA-966 on the neurochemical and behavioural responses to amphetamine have been determined in the mouse and rat. 2. In vehicle-treated control mice, (+)-HA-966 (30-100 mg kg-1) did not affect dopamine synthesis in either the nucleus accumbens or striatum and was without marked effect on spontaneous locomotor activity. ...
There is considerable evidence of interactions between adenosine A2A receptors and dopamine D2 receptors in striatal areas, and antagonists of the A2A receptor have been shown to reverse the motor effects of DA antagonists in animal models. The D2 antagonist haloperidol produces parkinsonism in humans, and ...
High affinity uptake of D-(/sup 3/H)aspartate, (/sup 3/H)choline and (/sup 3/H)GABA was examined in synaptosomal-containing preparations of rat nucleus accumbens septi 7 to 10 days after unilateral or bilateral N-methyl-D-aspartate lesions confined to the parataenial nucleus of the thalamus or the basolateral nucleus of the amygdala. Uptake of both D-(/sup 3/H)aspartate and ...
As human life expectancy continues to rise, financial decisions of aging investors may have an increasing impact on the global economy. In this study, we examined age differences in financial decisions across the adult life span by combining functional neuroimaging with a dynamic financial investment task. During the task, older adults made more suboptimal choices than younger ...
Spontaneous firing of ventral tegmental area (VTA) dopamine (DA) neurons provides ambient levels of DA in target areas such as the nucleus accumbens (NAc) and the prefrontal cortex (PFC). Here we report that the glial cell line-derived neurotrophic factor (GDNF), produced in one target region, the NAc, is retrogradely transported by DA neurons to the VTA where the growth ...
Functional imaging data were acquired during performance of a reward-contingency task in a unique cohort of adolescents (ages 14�18 years) who were characterized since infancy on measures of temperamental behavioral inhibition. Neural activation was examined in striatal structures (nucleus accumbens, putamen, caudate) with a known role in facilitating response to salient ...
This study examined the effects of norepinephrine (NE) and phentolamine on the electrical activities of pain-excited neurons (PENs) and pain-inhibited neurons (PINs) in the nucleus accumbens (NAc) of Wistar rats. Trains of electric pulses applied to the right sciatic nerve were used to provide noxious stimulation, and the discharges of PENs and PINs were recorded using a glass ...
Adenosine A2A antagonists can exert antiparkinsonian effects in animal models. Recent experiments studied the ability of MSX-3 (an adenosine A2A antagonist) to reverse the locomotor suppression and tremor produced by dopamine antagonists in rats. MSX-3 reversed haloperidol-induced suppression of locomotion, and reduced the tremulous jaw movements ...
Despite abundant expression of DNA methyltransferases (Dnmt�s) in brain, the regulation and behavioral role of DNA methylation remain poorly understood. We find that Dnmt3a expression is regulated in mouse nucleus accumbens (NAc) by chronic cocaine and chronic social defeat stress. Moreover, NAc specific manipulations that block DNA methylation potentiate cocaine reward and ...
Subsecond fluctuations in dopamine (dopamine transients) in the nucleus accumbens are often time-locked to rewards and cues and provide an important learning signal during reward processing. As the mesolimbic dopamine system undergoes dynamic changes during adolescence in the rat, it is possible that dopamine transients encode reward and stimulus presentations differently in ...
The release of endogenous dopamine and norepinephrine from six brain regions (cortex, hippocampus, hypothalamus, striatum, s. nigra, n. accumbens-o. tubercle) of chronically lead-exposed rats was compared to release from controls. Prenatal and postnatal chronic lead intoxication was induced by 1000 ppm lead acetate in the drinking water of dams 70 days prior to mating and ...
Caffeine is a behavioral stimulant consumed on a worldwide basis. The question of whether caffeine is addictive has been debated for over a decade. Caffeine acts as a mild positive reinforcer but is not consistently self-administered in humans or animals. With [14C]2-deoxyglucose autoradiography, we studied the effects of increasing doses of caffeine on cerebral glucose ...
The nucleus accumbens is a key mediator of cocaine reward, but the distinct roles of the two subpopulations of nucleus accumbens projection neurons, those expressing dopamine D1 vs. D2 receptors, are poorly understood. We show that deletion of TrkB, the brain-derived neurotrophic factor (BDNF) receptor, selectively from D1+ or D2+ neurons oppositely ...
In order to explore potential therapeutic implications of cannabinoid antagonists, the effects of the prototypical cannabinoid antagonist SR141716A on monoamine efflux from the medial prefrontal cortex and the nucleus accumbens of the rat were investigated by in vivo microdialysis.SR141716A moderately increased serotonin efflux and concentrations of its ...
M, Tirelli E (1999) Effects of nicotine administered via a transdermal delivery system on vigilance performance requires a task that markedly enhances accum- bens and basal forebrain activity. The literature by explicit delays between task onset and presentation of reward to enhance the moti- vational levels (Inglis
. Amphetamine (2.0 mg/kg, i.p), was systemically administered as a positive control in a fourth session, since-specific manner. Systemic amphetamine administra- tion significantly increased (100�200%) ACh in the PPC that amphetamine- induced ACh release does not involve transmission within NAC (Arnold et al., 2000). MATERIALS
et al., 2003). Synthesis of AMPA receptor subunits is increased after LTP and this process is PKA synthesis attenuates the expression of conditioned fear (Nader et al., 2000), and PKA activation-accumbens Rp- cAMPS blocks amphetamine-produced place conditioning in rats. Psychopharmacology 170
The purpose was to investigate whether activation of 5-HT1B receptors within the ventral tegmental area (VTA) facilitated dopamine (DA) transmission in the ipsilateral nucleus accumbens (NACC) and potentiated ethanol-induced increases in NACC DA by 5- HT1...
National Technical Information Service (NTIS)
Chronic stress contributes to vulnerability for depression and drug addiction. The function of the serotonergic system has been found to be modified by chronic stress and these changes may play an important role in stress-related relapses to drug craving. The 5-HT(1B) receptor is expressed in nucleus accumbens (NAc) projection neurons and modulates drug reward mechanisms and ...
