Learned associations between effects of abused drugs and the drug administration environment play important roles in drug addiction. Histochemical and electrophysiological studies suggest that these associations are encoded in sparsely distributed nucleus accumbens neurons that are selectively activated by drugs and drug-associated cues. Although ...

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 intra-accumbens infusion of glutamate ...

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 ...

A growing body of evidence suggests the existence of a functional interaction between gabapentin (GBP)-morphine system. However, the neuro-anatomical sites and molecular mechanism of action of gabapentin-morphine interaction to prevent and reverse morphine side effects as well as enhancement of the analgesic effect of morphine is not clear. Therefore, we examined the combined ...

The shell division of the nucleus accumbens receives noradrenergic input from neurons in the nucleus of the solitary tract (NTS) that transmit information regarding fluctuations in peripheral hormonal and autonomic activity. Accumbens shell neurons also receive converging inputs from limbic areas such as the ...

The shell division of the nucleus accumbens receives noradrenergic input from neurons in the nucleus of the solitary tract (NTS) that transmit information regarding fluctuations in peripheral hormonal and autonomic activity. Accumbens shell neurons also receive converging inputs from limbic areas such as the ...

We describe a 17-year-old girl with Kleine-Levin syndrome (KLS), in which gabapentin was effective for the prevention of attacks. (99)mTc-ECD SPECT revealed hyperperfusion of the thalamus and nucleus accumbens presenting in the symptomatic period, suggesting epilepsy-like neuronal discharge from these structures. Treatment for KLS has ...

Opiate withdrawal is associated with morphological changes of dopamine neurons in the ventral tegmental area and with reduction of spine density of second-order dendrites of medium size spiny neurons in the nucleus accumbens shell but not core. Withania somnifera has long been used in the Middle East, Africa, and India as a remedy for ...

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. ...

The nucleus accumbens (NAc) is a critical element of the mesocorticolimbic system, a brain circuit implicated in reward and motivation. This basal forebrain structure receives dopamine (DA) input from the ventral tegmental area (VTA) and glutamate (GLU) input from regions including the prefrontal cortex (PFC), amygdala (AMG), and hippocampus (HIP). As such, it integrates ...

The midbrain ventral tegmental area (VTA) projection to the nucleus accumbens (NAc) is implicated in motivation and reinforcement. A significant number of NAc medium spiny neurons (MSNs) project back to the VTA, although the nature of this projection is essentially unknown. For example, do NAc MSNs directly target accumbens-projecting ...

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 ...

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 ...

The striatum is considered to be critical for the control of goal-directed action, with the lateral dorsal striatum (latDS) being implicated in modulation of habits and the nucleus accumbens thought to represent a limbic�motor interface. Although medium spiny neurons from different striatal subregions exhibit many similar properties, differential firing ...

The closely related ? and ? isoforms of the serine/threonine protein kinase casein kinase 1 (Csnk1) have been implicated in the generation of psychostimulant-induced behaviors. In this study, we show that Csnk1?/? produces its effects on behavior by acting on the Darpp-32-PP1 signaling pathway to regulate AMPA receptor phosphorylation in the nucleus accumbens (NAcc). ...

The interoceptive effects of alcohol are major determinants of addiction liability. Metabotropic glutamate (mGlu) receptors are widely expressed in striatal circuits known to modulate drug-seeking. Given that the interoceptive effects of drugs can be important determinants of abuse liability, we hypothesized that striatal mGlu receptors modulate the interoceptive effects of alcohol. Using drug ...

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+ ...

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) decreased extracellular ...

Rats were implanted with recording electrodes aimed at the subiculum and nucleus accumbens. They were subsequently placed in a cylindrical environment, where they searched for locations where they would receive rewarding medial forebrain bundle stimulation. At times a tone was sounded, indicating that the reward location was in the center of the environment. Animals quickly ...

Aversive states are proposed to drive addiction. Here, Wheeler and colleagues show that drug-associated cues come to activate neural representations of aversive information in nucleus accumbens and that this activation predicts subsequent drug use. These remarkable data identify a potential neural substrate through which aversive affective representations may motivate drug ...

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 ...

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 ...

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. Extracellular signal-regulated kinase ...

Signaling through N-methyl-D-aspartate-type glutamate receptors (NMDARs) is essential for the development of behavioral sensitization to psychostimulants such as amphetamine (AMPH). However, the cell type and brain region in which NMDAR signaling is required for AMPH sensitization remain unresolved. Here we use selective inactivation of Grin1, the gene encoding the essential NR1 subunit of NMDARs, ...

Signaling through N-methyl-d-aspartate�type glutamate receptors (NMDARs) is essential for the development of behavioral sensitization to psychostimulants such as amphetamine (AMPH). However, the cell type and brain region in which NMDAR signaling is required for AMPH sensitization remain unresolved. Here we use selective inactivation of Grin1, the gene encoding the essential NR1 subunit of ...

Many motivated and addiction-related behaviors are sustained by activity of both dopamine D1- and D2-type receptors (D1Rs and D2Rs) as well as CB1 receptors (CB1Rs) in the nucleus accumbens (NAc). Here, we use in vitro whole-cell patch-clamp electrophysiology to describe an endocannabinoid (eCB)-dopamine receptor interaction in adult rat NAc core neurons. ...

Both hemispheric bias and sex differences exist in striatal-mediated behaviors and pathologies. The extent to which these dimorphisms can be attributed to an underlying neuroanatomical difference is unclear. We therefore quantified neuron soma size and density in the dorsal striatum (CPu) as well as the core (AcbC) and shell (AcbS) subregions of the nucleus ...

Maternal infection during pregnancy has been associated with increased incidence of schizophrenia in the adult offspring. Mechanistically, this has been partially attributed to neurodevelopmental disruption of the dopamine neurons, as a consequence of exacerbated maternal immunity. In the present study we sought to target hypoferremia, a cytokine-induced reduction of serum ...

There is significant pharmacological and behavioral evidence that group I metabotropic glutamate receptors (mGluR1a and mGluR5) in the nucleus accumbens play an important role in the neurochemical and pathophysiological mechanisms that underlie addiction to psychostimulants. To further address this issue, we undertook a detailed ultrastructural analysis to characterize changes ...

The objective of these studies was to pharmacologically characterize the mechanism responsible for a folate-induced stimulation of locomotor activity in rats after bilateral injection into the nucleus accumbens region of the brain. Folic acid (FA) and 5-formyltetrahydrofolic acid (FTHF) produced this hypermotility response after intra-accumbens injection, ...

Oxytocin receptors in the nucleus accumbens have been implicated in the regulation of alloparental behavior and pair bond formation in the socially monogamous prairie vole. Oxytocin receptor density in the nucleus accumbens is positively correlated with alloparenting in juvenile and adult female prairie voles, and oxytocin receptor antagonist infused into ...

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

Neuronal circuits including medium spiny neurons (MSNs) in the nucleus accumbens (NAc) and melanin-concentrating hormone (MCH)-containing neurons in the lateral hypothalamic area (LHA) are hypothesized to play an important role in hedonic feeding. A reciprocal connection between NAc MSNs and MCH-containing ...

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 ...

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 ...

Lesion of mesolimbic dopaminergic neurons induces hypoactivity and hypo-exploration in a new environment, lack of hyperactivity to amphetamine and hyperresponsiveness to apomorphine. Transplantation of embryonic dopaminergic cells from rat embryos into the deafferented nucleus accumbens restores, 8 weeks after grafting, some of the deficits obtained after ...

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 ...

Cholinergic neurons were studied by immunohistochemistry with an antiserum against human choline acetyltransferase in the caudate nucleus, putamen, and ventral striatum (including the nucleus accumbens) of three patients with Alzheimer disease and three control subjects. Immunoreactive cell bodies were mapped and counted. In the ventral striatum of ...

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 drugs. ...

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 (increased responsiveness of dopamine Dl ...

Neuron Report Coordinated Accumbal Dopamine Release and Neural Activity Drive Goal such as the nucleus accumbens (NAc). However, a direct role of dopamine in ICSS-mediated reward has been questioned that, at certain sites, the onset of anticipatory dopamine surges and changes in neuronal firing

. Such aversive states are proposed to incline the addict toward further drug use (Koob and Le Moal, 2001; Solomon learn to avoid taste cues that are predictive of addictive drugs (Grigson and Twining, 2002; Wise et al@schoenbaumlab.org DOI 10.1016/j.neuron.2008.02.025 Aversive states are proposed to drive addiction. Here, Wheeler

Many studies have suggested that the behavioral and reinforcing effects of morphine are induced by hyperactivation of the mesolimbic dopaminergic system, which results in increases in locomotor activity, c-Fos expression in the nucleus accumbens (NAc), and tyrosine hydroxylase (TH) in the ventral tegmental area (VTA). In order to investigate the effect of wild ginseng (WG) on ...

The function of 5-HT6 receptors, one of the last additions to the large family of 5-HT receptors, is largely unknown due to the limited knowledge of their transduction mechanisms, lack of full centrally acting agonists and inconsistencies in the pharmacological and neurochemical effects of the antagonists. Recently, a new full agonist, ST1936, with nanomolar affinity for 5-HT6 receptors, has ...

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. ...

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. ...

The open channel N-methyl-D-aspartate (NMDA) receptor antagonists dizocilpine (MK-801) and phencyclidine (PCP) increase the firing rate of both A9 and A10 dopaminergic neurons in the rat. In the A10 nucleus, this effect of MK-801 is reportedly prevented by either competitive NMDA antagonists or serotonin2 (5-HT2) antagonists. The present study examined the ...

The major projection cells of the nucleus accumbens (NAc) are under a strong inhibitory influence from GABAergic afferents and depend on afferent excitation to produce their output. We have earlier reported that substance P (SP), a peptide which is colocalized with GABA in these neurons, depresses excitatory synaptic transmission in this nucleus (Kombian, ...

The involvement of dopamine within the nucleus accumbens in the formation and maintenance of pair bonds was assessed in a series of experiments using the monogamous prairie vole. We show that dopamine transmission that promotes pair bond formation occurs within the rostral shell of the nucleus accumbens, but not in its core or caudal shell. Within this ...

Administration of either Tyr-D-Ala-Gly-MePhe-Gly(ol) (DAGO), a mu-opioid agonist, or nicotine into the VTA (A10) caused an increase in both dopamine (DA) and its metabolite levels in both the A10 region and DA nerve terminals in the nucleus accumbens of rats when assessed with dual probe brain dialysis. These findings show that DAGO and nicotine increase both axonal- and ...

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 ...

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 dose of ...

Addictive drugs cause persistent restructuring of several neuronal cell types in the brain�s limbic regions thought to be responsible for long-term behavioral plasticity driving addiction. Although these structural changes are well documented in nucleus accumbens medium spiny neurons, little is known regarding the underlying ...

Estradiol affects a variety of brain regions by modulating physiological and cellular functions as well as neuronal morphology. Within the striatum, estradiol is known to induce physiological and molecular changes, yet estradiol's effects on striatal dendritic morphology have not yet been evaluated. Using ballistic delivery of the lipophilic dye DiI to tissue sections, we were ...

Estradiol affects a variety of brain regions by modulating physiological and cellular functions as well as neuronal morphology. Within the striatum, estradiol is known to induce physiological and molecular changes, yet estradiol�s effects on striatal dendritic morphology have not yet been evaluated. Using ballistic delivery of the lipophilic dye DiI to tissue sections, we ...

The involvement of metabotropic glutamate receptors type 5 (mGluR5) in drug-induced behaviours is well-established but limited information is available on their functional roles in addiction-relevant brain areas like the nucleus accumbens (NAc). This study demonstrates that pharmacological and synaptic activation of mGluR5 increases the spike discharge of medium spiny ...

The present study examines subcortical connections of Pa, following small anterograde and retrograde tracer injections in cynomolgus monkeys (Macaca fascicularis). An anterograde tracer injection into the dorsal midline thalamus revealed strong projections to the accumbens nucleus, basal amygdala, lateral septum, and hypothalamus. Retrograde tracer injections into these areas ...

Lead treatment via drinking water for 3 to 6 weeks at 250 ppm was found to significantly decrease the number of spontaneously active dopamine (DA) neurons in both the substantia nigra and ventral tegmental area that were recorded using standard extracellular electrophysiological recording techniques. Lead exposure did not affect the discharge rate or discharge pattern of these ...

The abuse of anabolic androgenic steroids (AS) is a growing problem; however, the effects and mechanisms underlying their addictive effects are not well understood. Research findings regarding androgen abuse in people and hedonic effects of androgens in laboratory rats are reviewed. Androgens, like other steroids, can have traditional actions via cognate intracellular steroid receptors, as well as ...

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 ...

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 ...

A major limitation of neural transplantation studies is assessing the degree of host-graft interaction. In the present study, rat hippocampal/cortical embryonic neurons (E18) were infected with a lentivirus encoding enhanced green fluorescent protein (GFP) under control of the neuron-specific synapsin promoter thus permitting robust identification of ...

Neural encoding of cocaine-seeking behavior is coincident with phasic dopamine release, neurotransmission, rat, reward Abstract Mesolimbic dopamine neurons projecting from the ventral tegmental area, the precise role of rapid (subsecond) dopamine release within the primary subregions of the NAc (the core

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

with special reference to the basal ganglia, studied in the rat by anterograde and retrograde transport compacta neurons in an in vitro slice preparation. Brain Res. 372: 21�30, 1986. LACEY, M. G., MERCURI, N. B. Monosynaptic input from the nucleus accumbens-ventral striatum region to retrogradely labelled nigrostriatal

The present study investigated the effect of prenatal stress (PS) on juvenile behavior and adult amphetamine (AMPH) sensitization, as well as the effect of the interaction between experience (i.e. PS) and drug (i.e. AMPH) on cortical thickness and neuronal morphology in corticolimbic regions in rats. Juvenile male and female rats, exposed to gestational stress, were tested in ...

Our previous investigation demonstrated that repeated administration of morphine significantly enhanced ?(2)/?-1 subunit expression in the frontal cortex and limbic forebrain of mice as well as morphine-induced place preference. However, little is known about regulatory mechanisms of ?(2)/?-1 subunit expression in conditioned place preference by methamphetamine (METH). In the present study, we ...

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 target areas, but no Fos-positive ...

Cholinergic neurons are widespread, and pharmacological modulation of acetylcholine receptors affects numerous brain processes, but such modulation entails side effects due to limitations in specificity for receptor type and target cell. As a result, causal roles of cholinergic neurons in circuits have been unclear. We integrated optogenetics, freely ...

Loss of dopamine neurons in experimental parkinsonism results in altered cyclic nucleotide cAMP and cGMP levels throughout the basal ganglia. Our objective was to examine whether expression of phosphodiesterase 10A (PDE10A), an isozyme presenting a unique distribution in basal ganglia, is altered after unilateral injection of 6-hydroxydopamine in the medial forebrain bundle, ...

The hypocretin/orexin (HCRT) neuropeptide system modulates behavioral state and state-dependent processes via actions on multiple neuromodulatory transmitter systems. Recent studies indicate that HCRT selectively increases dopamine (DA) neurotransmission within the prefrontal cortex (PFC) and the shell subregion of the nucleus accumbens (NAs), but not the core subregion of the ...

Orexin/hypocretin neurons in the lateral hypothalamus and adjacent perifornical area (LH/PFA) innervate midbrain dopamine (DA) neurons that project to corticolimbic sites and subserve psychostimulant-induced locomotor activity. However, it is not known whether dopamine neurons in turn regulate the activity of orexin cells. We examined ...

Mesoventromedial dopamine neurons projecting from the medial ventral tegmental area to the ventromedial shell of the nucleus accumbens play a role in attributing incentive salience to environmental stimuli that predict important events, and appear to be particularly sensitive to the effects of psychostimulant drugs. Despite the observation that these ...

The nucleus accumbens (NAc) is positioned to integrate signals originating from limbic and cortical areas and to modulate reward-related motor output of various goal-directed behaviours. The major target of the NAc GABAergic output neurons is the ventral pallidum (VP). VP is part of the reward circuit and controls the ascending mesolimbic dopamine system, ...

The weaver mouse represents the only genetic animal model of gradual nigrostriatal dopaminergic neurodegeneration which is proposed as a pathophysiological phenotype of Parkinson's disease. The aim of the present study was to analyze the nitric oxide and dopaminergic systems in selected brain regions of homozygous weaver mice at different postnatal ages corresponding to specific stages of the ...

SUMMARYLeptin acts via its receptor (LepRb) to regulate neural circuits in concert with body energy stores. In addition to acting on a number of hypothalamic structures, leptin modulates the mesolimbic dopamine (DA) system. To determine the sites at which LepRb neurons might directly influence the mesolimbic DA system, we examined the distribution of LepRb ...

The neurotransmitter dopamine (DA) is essential for learning in a Pavlovian fear conditioning paradigm known as fear-potentiated startle (FPS). Mice lacking the ability to synthesize DA fail to learn the association between the conditioned stimulus and the fear-inducing footshock. Previously, we demonstrated that restoration of DA synthesis to neurons of the ventral tegmental ...

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 ...

neurons and trained links between excitatory and inhibitory neurons. They use inhibition to prevent,e is the weight of the projection of the eth excitatory neuron onto the ith inhibitory neuron with possible values is roughly 0.2. The R- net modeled for this paper has 40% of excitatory ...

The impact of paternal care on the postnatal development of inhibitory neuronal subpopulations in prefrontal and limbic brain regions was studied in the rodent Octodon degus. Comparing offspring from biparental families with animals raised by a single mother revealed region-specific deprivation-induced changes in the density of PARV- and CaBP-D28k expressing cells. Some ...

Although the core region of the nucleus accumbens (NAcc) has been implicated in motor control and the acquisition of appetitive learning, these processes are altered by environmental experience. To assess how environment influences neuronal processing in NAcc core, we recorded single-unit activity during acquisition of an appetitive learning task in which ...

In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self-administration sessions are ...

In the cocaine self-administering rat, individual nucleus accumbens (NAcc) neurons exhibit phasic changes in firing rate within minutes and/or seconds of lever presses (i.e. slow phasic and rapid phasic changes, respectively). To determine whether neurons that demonstrate these changes during self-administration sessions are ...

In the frog Discoglossus pictus and the salamander Plethodon jordani, the morphology and axonal projection pattern of neurons in the medial and dorsal pallium were determined by intracellular biocytin labeling. A total of 77 pallial neurons were labeled in the frog and 58 pallial neurons in the salamander. Within the medial pallium ...

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 ...

Basal ganglia circuits are organized as parallel loops that have been proposed to compete in a winner-take-all fashion to determine the appropriate behavioral outcome. However, limited experimental support for strong lateral inhibition mechanisms within striatal regions questions this model. Here, stimulation of the prefrontal cortex (PFC) using naturally occurring bursty patterns inhibited firing ...

The striatum, the first relay of the basal ganglia system, is critically involved in motor functions and motivational processes. The dorsal striatum is central to the motor control and motor learning and the ventral striatum or nucleus accumbens is essential for motivation, the reward system and reinforcement by drugs. This system is dysfunctional in movement disorders such as ...

NAc inactivation increases food intake, indicating that NAc neurons exert ongoing inhibition of feeding. We previously described a subpopulation of NAc neurons that pause during sucrose licking and proposed that the pause permits consumption. We tested this hypothesis by first recording NAc neurons during sucrose consumption, and then ...

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 ...

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 extracellular level of ...

Administration of opioid drugs such as heroin produces several immunosuppressive effects, including decreases in natural killer (NK) cell activity, lymphocyte proliferative responses, and nitric oxide production. Interestingly, opioids have been shown to alter many immune parameters indirectly by modulating the immunoregulatory actions of the central nervous system. Recently, it has been ...

Administration of opioid drugs such as heroin produces several immunosuppressive effects, including decreases in natural killer (NK) cell activity, lymphocyte proliferative responses, and nitric oxide production. Interestingly, opioids have been shown to alter many immune parameters indirectly by modulating the immunoregulatory actions of the central nervous system. Recently, it has been ...

In humans, exposure to environmental contexts previously associated with heroin intake can provoke drug relapse, but the neuronal mechanisms mediating this relapse are unknown. Using a drug relapse model, we found previously that reexposing rats to heroin-associated contexts, after extinction of drug-reinforced responding in different contexts, reinstates heroin seeking. This ...

Inbred Lewis and Fisher 344 rat strains differ greatly in drug self-administration; Lewis rats operantly self-administer drugs of abuse including nicotine, whereas Fisher self-administer poorly. As shown herein, operant food self-administration is similar. On the basis of their pivotal role in drug reward, we hypothesized that differences in basal gene expression in GABAergic ...

Drug-induced malfunction of nucleus accumbens (NAc) neurons underlies a key pathophysiology of drug addiction. Drug-induced changes in intrinsic membrane excitability of NAc neurons are thought to be critical for producing behavioral alterations. Previous studies demonstrate that, after short-term (2 d) or long-term (21 d) withdrawal ...

BackgroundThe striatal complex is the major target of dopamine action in the CNS. There, medium-spiny GABAergic neurons, which constitute about 95% of the neurons in the area, form a mutually inhibitory synaptic network that is modulated by dopamine. When put in culture, the neurons reestablish this network. In particular, they make ...

The encoding of reward-predictive stimuli by neurons in the nucleus accumbens (NAcc) depends on integrated synaptic activity from the basolateral amygdala (BLA) and medial prefrontal cortex (mPFC) afferent inputs. In a previous study, we found that single electrical stimulation pulses applied to the BLA facilitate mPFC-evoked spiking in NAcc ...

The current study aimed to further elucidate the role of endocannabinoid signaling in methamphetamine-induced psychomotor activation. Rats were treated with bilateral, intracranial microinjections of the cannabinoid CB1 receptor antagonists rimonabant (1 ?g; 1 ?l) or AM251 (1 ?g; 1 ?l), or vehicle (1 ?l), followed by intravenous methamphetamine (3 mg/kg). Antagonist pretreatment in the nucleus ...

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 ...

Anatomical and functional refinements of the meso-limbic dopamine system of the rat are discussed. Present experiments suggest that dopaminergic neurons localized in the posteromedial ventral tegmental area (VTA) and central linear nucleus raphe selectively project to the ventromedial striatum (medial olfactory tubercle and medial nucleus accumbens shell), ...

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 into nucleus ...

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 brain region. This ...

Neurons in a small number of brain structures detect rewards and reward-predicting stimuli and are active during the expectation of predictable food and liquid rewards. These neurons code the reward information according to basic terms of various behavioural theories that seek to explain reward-directed learning, approach behaviour and decision-making. The ...

To explore the functional consequences of cannabinoid withdrawal in the rat mesolimbic dopamine system, we investigated the anatomical morphology of the mesencephalic, presumed dopaminergic, neurons and their main post-synaptic target in the Nucleus Accumbens. We found that TH-positive neurons shrink and Golgi-stained medium spiny ...

Striatal dopamine (DA) and acetylcholine (ACh) regulate motivated behaviors and striatal plasticity. Interactions between these neurotransmitters may be important, through synchronous changes in parent neuron activities and reciprocal presynaptic regulation of release. How DA signalling is regulated by striatal muscarinic receptors (mAChRs) is unresolved; contradictory reports ...

Striatal dopamine (DA) and acetylcholine (ACh) regulate motivated behaviors and striatal plasticity. Interactions between these neurotransmitters may be important, through synchronous changes in parent neuron activities and reciprocal presynaptic regulation of release. How DA signaling is regulated by striatal muscarinic receptors (mAChRs) is unresolved; contradictory reports ...

The basal ganglia system is thought to play a key role in the control of absence-seizures and there is ample evidence that epileptic seizures modify brain dopamine function. We recently reported that local injections of dopamine D1 or D2 agonists in the core of the nucleus accumbens suppressed absence-seizures in a spontaneous, genetic rodent model of absence-epilepsy whereas ...

Little is known regarding the involvement of the ventral pallidum (VP) in cocaine-seeking behavior, in contrast with considerable documentation of the involvement of its major afferent, the nucleus accumbens, over the past thirty years utilizing electrophysiology, lesion, inactivation, molecular, imaging, and other approaches. The VP is neuroanatomically positioned to ...

Little is known regarding the involvement of the ventral pallidum (VP) in cocaine-seeking behavior, in contrast with considerable documentation of the involvement of its major afferent, the nucleus accumbens, over the past thirty years utilizing electrophysiology, lesion, inactivation, molecular, imaging, and other approaches. The VP is neuroanatomically positioned to ...

Spontaneous development of lupus-like disease in MRL-lpr mice is accompanied by a constellation of behavioral deficits, including blunted responsiveness to sucrose. Although autoimmunity-induced damage of limbic areas is proposed to underlie this deficit, the systemic nature of the disease precludes inference of a causal relationship between CNS damage and functional loss. Based on the stimulatory ...

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 ...

Dopamine (DA) neurons in the substantia nigra (SN) and ventral tegmental area (VTA) form several projection systems with diverse functions, such as motor planning through the striatum, reward seeking via the nucleus accumbens (NAc), and cognitive control through the prefrontal cortex (PFC). Disruptions in DA cell activity profoundly impair these functions ...

In situ hybridization experiments were performed with brain sections from normal, control and haloperidol-treated rats to identify and map the cells expressing the D2 dopamine receptor gene. D2 receptor mRNA was detected with radioactive or biotinylated oligonucleotide probes. D2 receptor mRNA was present in glandular cells of the pituitary intermediate lobe and in neurons of ...

Apamin is a neurotoxin extracted from honey bee venom and is a selective blocker of small-conductance Ca(2+) -activated K(+) channels (SK). Several behavioral and electrophysiological studies indicate that SK-blockade by apamin may enhance neuron excitability, synaptic plasticity, and long-term potentiation in the CA1 hippocampal region, and, for that reason, apamin has been ...

Leptin acts in the brain to prevent obesity. The underlying neurocircuitry responsible for this is poorly understood, in part because of incomplete knowledge regarding first-order, leptin-responsive neurons. To address this, we and others have been removing leptin receptors from candidate first-order neurons. While functionally ...

Nucleus accumbens (NAc) neurons are excited primarily by AMPA-type glutamate receptors (AMPAR). This is required for cocaine seeking in animal models of cocaine addiction, suggesting AMPAR transmission in the NAc as a key control point for cocaine-related behaviors. This review will briefly describe AMPAR properties and trafficking, with a focus on studies ...

Tobacco use is a major public health problem, and although many smokers report that they want to quit, only a small percentage succeed. Side effects associated with nicotine withdrawal, including depression, anxiety, and restlessness, certainly contribute to the low success rate. The dorsal raphe nucleus (DRN) is a serotonergic center with many functions, including control of mood and emotional ...

Drug-induced malfunction of nucleus accumbens (NAc) neurons underlies a key pathophysiology of drug addiction. Drug-induced changes in intrinsic membrane excitability of NAc neurons are thought to be critical for producing behavioral alterations. Previous studies demonstrate that following short-term (2d) or long-term (21d) withdrawal ...

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 ...

The endocannabinoid system regulates neurotransmission in brain regions relevant to neurobiological and behavioral actions of addicting drugs. We recently demonstrated that inhibition by URB597 of fatty acid amide hydrolase (FAAH), the main enzyme which degrades the endogenous cannabinoid N-acylethanolamine (NAE) anandamide and the endogenous non-cannabinoid NAEs oleoylethanolamide and ...

Coincident signaling by dopamine and glutamate is thought to be crucial for a variety of motivated behaviors. Previous work has suggested that some midbrain dopamine neurons are themselves capable of glutamate co-release, but this phenomenon remains poorly understood. Here, we expressed the light-activated cation channel Channelrhodopsin-2 (ChR2) in genetically defined ...

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 ...

Studies have demonstrated the changes of the physiological characteristics of nucleus accumbens (NAc) neurons with the postnatal development of rats. In the present study, spontaneous excitatory postsynaptic currents (sEPSCs) were recorded in the slices of NAc shell (NAcS) of adult and juvenile rats. Our results demonstrate that both the average amplitude ...

Patterns of immunoreactivity for calcium-binding protein, tyrosine hydroxylase and four neuropeptides in the ventral striatum (nucleus accumbens, olfactory tubercle and ventromedial parts of the caudate nucleus and putamen) were compared to patterns of these markers in the dorsal striatum (the majority of the neostriatum) in rhesus monkey. The striatal mosaic was delineated by ...