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 ...
E-print Network
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 ...
PubMed
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 ...
PubMed Central
Recent evidence demonstrated that dopamine within the nucleus accumbens mediates consolidation of both associative and nonassociative memories. However, the specific contribution of the nucleus accumbens subregions, core and shell, and of D1 and D2 receptors subtypes has not been yet clarified. The aim of this ...
ERIC Educational Resources Information Center
Although progress has been made identifying neural mechanisms underlying ethanol's primary reinforcing effects, few studies have examined the mechanisms mediating ethanol-induced conditioned effects. A recent lesion study suggests that expression of ethanol-conditioned behaviors depends upon an intact amygdala and nucleus accumbens ...
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 ...
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 ...
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 ...
Latent inhibition (LI) manifests as poorer conditioning to a CS that has previously been presented without consequence. There is some evidence that LI can be potentiated by reduced mesoaccumbal dopamine (DA) function but the locus within the nucleus accumbens of this effect is as yet not firmly established. Experiment 1 tested whether 6-hydroxydopamine (6-OHDA)-induced lesions ...
A distributed limbic-corticostriatal circuitry is implicated in cue-induced drug craving and relapse. Exposure to drug-paired cues not only precipitates relapse, but also triggers the reactivation and reconsolidation of the cue-drug memory. However, the limbic cortical-striatal circuitry underlying drug memory reconsolidation is unclear. The aim of this study was to investigate the involvement of ...
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 ...
Tests of Pavlovian-instrumental transfer (PIT) demonstrate that reward-predictive stimuli can exert a powerful motivational influence on the performance of instrumental actions. Recent evidence suggests that predictive stimuli produce this effect through either the general arousal (general PIT) or the specific predictions (outcome-specific PIT) produced by their association with reward. In two ...
Although it has long been hypothesized that the nucleus accumbens (NAc) acts as an interface between limbic and motor regions, direct evidence for this modulatory role on behavior is lacking. Using a disconnection procedure in rats, we found that basolateral amygdala (BLA) input to the core and medial shell of the NAc separately ...
Professor Trevor Robbins explains that the reward system, where dopamine mediates messages to the nucleus accumbens, is artificially activated by certain drugs.
NSDL National Science Digital Library
Alcohol has subjective and behavioral effects at the pharmacological levels typically reached during the consumption of one or two alcoholic drinks. Here we provide evidence that an ?4-subunit-containing gamma-amino-butyric acid A (GABAA) receptor contributes to the consumption of low-to-moderate levels of alcohol. Using viral-mediated RNA-interference ...
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 utilization in rats. At 1 ...
Pavlovian stimuli previously paired with food can markedly elevate the rate of food-reinforced instrumental responding. This effect, termed Pavlovian-instrumental transfer (PIT), depends both on general activating and specific cueing properties of Pavlovian stimuli. Recent evidence suggests that the general activating properties of Pavlovian stimuli are mediated by ...
BackgroundThe neural substrates regulating sensorimotor gating in rodents are studied in order to understand the basis for gating deficits in clinical disorders such as schizophrenia. N-methyl-d-aspartate (NMDA) infusion into the ventral temporal lobe, including caudal parts of the ventral hippocampal region and amygdala, has been shown to disrupt sensorimotor gating in rats, as measured by ...
Conditioned responding to drug-predictive discrete cues can be strongly modulated by drug-associated contexts. We tested the hypothesis that differential recruitment of the nucleus accumbens (NAc) core and shell mediates responding to drug cues in a drug vs non-drug context. Rats were trained to discriminate between two 10-s auditory ...
, Milford, MA), and radioactivity measurements were obtained with a calibrated ion chamber (Capintec, Ramsey
Oxytocin receptors (OTR) and vasopressin V1a receptors (V1aR) in the ventral forebrain play critical roles in the formation of pair bonds in the monogamous prairie vole. Previous reports have been inconsistent in the identification of the specific brain regions in the ventral forebrain that express these receptors. To delineate more clearly the neuroanatomical boundaries of the OTR and V1aR fields ...
The quinpirole sensitization model of obsessive-compulsive disorder was used to investigate the functional role that brain regions implicated in a neuroanatomical circuit of obsessive-compulsive disorder may play in compulsive checking behavior. Following repeated injections of saline or quinpirole (0.5mg/kg, twice per week, �8 injections) to induce compulsive checking, rats received ...
Estrogen enhances psychostimulant-induced dopamine receptor-mediated behaviors. One possible mechanism for this enhancement is modulation of the expression of the regulators of G-protein signaling (RGS) proteins. Ovariectomized (OVX) rats received empty s.c. implants or implants packed with 17beta estradiol. Two weeks later the rats were given a single injection of various ...
Relapse to drug seeking was studied using a rodent model of reinstatement induced by exposure to drug-related cues. The mammalian target of rapamycin (mTOR), a serine/threonine protein kinase that regulates cell growth and survival by controlling translation in response to nutrients and growth factors, has been demonstrated to be involved in neuronal adaptations that underlie drug addiction and ...
RationaleKappa opioid receptors (KORs) have been implicated in depressive-like states associated with chronic administration of drugs of abuse and stress. Although KOR agonists decrease dopamine in the nucleus accumbens (NAc), KOR modulation of phasic dopamine release in the core and shell subregions of the NAc�which have distinct roles in reward ...
RationaleIn humans, exposure to environmental contexts previously associated with heroin intake can provoke relapse to drug use. In rats, exposure to heroin-associated contexts after extinction of drug-reinforced responding in different contexts reinstates heroin seeking. This effect is attenuated by blockade of D1-family receptors in lateral or medial ...
Lack of Cocaine Effect on Dopamine Clearance in the Core and Shell of the Nucleus Accumbens Carolina 27157 Cocaine produces its reinforcing effects primarily by inhibiting the dopamine transporter). Surprisingly, in mice genetically lacking the DAT, cocaine was still able to elevate DA in the nucleus
As a ubiquitous serine/threonine protein kinase, glycogen synthase kinase 3? (GSK-3?) has been considered to be important in the synaptic plasticity that underlies dopamine-related behaviors and diseases. We recently found that GSK-3? activity in the nucleus accumbens (NAc) core is critically involved in cocaine-induced behavioral sensitization. The ...
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 ...
Mesolimbic dopamine neurons projecting from the ventral tegmental area (VTA) to the nucleus accumbens (NAc) are part of a complex circuit mediating cocaine-directed behaviors. However, the precise role of rapid (subsecond) dopamine release within the primary sub-regions of the NAc, the core and shell, and its relationship to NAc cell ...
The present study investigated the central effects of the selective serotonin reuptake inhibitor (SSRI) fluoxetine and the role of 5-hydroxytryptamine3 (5-HT3) receptors in the core of the nucleus accumbens (NAc) on cocaine-induced behavioural changes in rats.The 5-HT3 receptor antagonist ...
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 ...
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 hippocampus and amygdala that process newly ...
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, ...
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While knowing what to expect is important, it is equally important to know when to expect it and to respond accordingly. This is apparent even in simple Pavlovian training situations in which animals learn to respond more strongly closer to reward delivery. Here we report that the nucleus accumbens core, an area well-positioned to represent information ...
Plasticity in the Nucleus Accumbens Derek A. Hamilton and Bryan Kolb University of Lethbridge Drugs and other a core theoretical concept in the neurosciences (Greenough & Bailey, 1988; Kolb & Whishaw, 1998; Kolb, Forgie, Gibb, Gorny, & Rowntree, 1998; Kolb & Whishaw, 1998; van Pragg, Kempermann, & Gage, 2000
Dopamine receptors (DARs) in the nucleus accumbens (NAc) are critical for cocaine's actions but the nature of adaptations in DAR function after repeated cocaine exposure remains controversial. This may be due in part to the fact that different methods used in previous studies measured different DAR pools. In the present study, we used a protein crosslinking assay to make the ...
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. ...
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 great deal of behavioral and economic research suggests that the value attached to a reward stands in inverse relation to the amount of effort required to obtain it, a principle known as effort discounting. In the current report, we present the first direct evidence for a neural analogue of effort discounting. Functional magnetic resonance imaging was used to measure neural responses to monetary ...
Four experiments examined the effects of an infusion of morphine into the accumbens nucleus upon the aversive conditioning that can occur in rats exposed to the heated floor of a hot-plate apparatus. An infusion of morphine into the accumbens nucleus but not into the caudoputamen or into the prefrontal cortex impaired the acquisition of a conditioned ...
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 ...
ObjectiveTo test the hypothesis that mu-opioid receptor signaling in the nucleus accumbens contributes to hedonic (over)eating and obesity. To investigate the effects of chronic mu-opioid antagonism in the nucleus accumbens core or shell on intake of a palatable diet, and the development of diet-induced obesity in rats.Methods and ...
Ca2+/calmodulin-dependent protein kinase II (CaMKII) is known to contribute to the expression of psychostimulant sensitization by regulating dopamine (DA) overflow from DA neuron terminals in the nucleus accumbens (NAcc). The present experiments explored the contribution of CaMKII in NAcc neurons postsynaptic to these terminals where it is known to ...
BackgroundA previous study indicated that selectively bred alcohol-preferring (P) rats self-administered ethanol (EtOH) directly into the posterior ventral tegmental area at lower concentrations than Wistar rats. The present study was undertaken to determine involvement of the nucleus accumbens (Acb) with EtOH reinforcement, and a relationship between genetic selection for ...
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 ...
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 ...
The functional integrity of the nucleus accumbens (NAC) core and shell is necessary for contextual cocaine-seeking behavior in the reinstatement animal model of drug relapse; however, the neuropharmacological mechanisms underlying this phenomenon are poorly understood. The present study evaluated the contribution of metabotropic glutamate receptor subtype ...
Corticosteroid receptor modulation of mesoaccumbens dopamine neurotransmission is believed to be a key neurobiological mechanism mediating the effects of stress in addiction. Importantly, nucleus accumbens (NAc) subregions (core and shell) are reported to respond differentially to fluctuating basal levels of glucocorticoids, with ...
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 ...
The nucleus accumbens (Acb) is an extensively studied neuroanatomical substrate of opiate reward and the neural plasticity associated with chronic opioid use. The cellular mechanisms mediating opioid-dependent plasticity are uncertain, however AMPA-type glutamate receptor trafficking in dopamine D1 dopamine receptor (D1R) expressing neurons may be a ...
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 neurochemical, behavioral, and cognitive effects of the benzodiazepine receptor partial inverse agonist beta-carboline FG 7142 (FG), a drug traditionally described as exhibiting 'anxiogenic' effects, are proposed to model core components of present theories of the neuronal mechanisms of schizophrenia. FG activates the mesolimbic dopaminergic system and, via increases in ...
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 ...
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 ...
Cocaine induces plasticity at glutamatergic synapses in the nucleus accumbens (NAc). Withdrawal was suggested to play an important role in the development of this plasticity by studies showing that some changes only appear several weeks after the final cocaine exposure. In this study, the requirement for prolonged withdrawal was evaluated by comparing the changes in ...
Interactions between the opioidergic and dopaminergic systems in the nucleus accumbens (NAcb) play a critical role in mediating cocaine withdrawal-induced effects on cell signaling and behavior. In support of this, increased activation of striatal dopamine-D1 receptors (D1R) results in desensitization of delta-opioid receptor (DOR) signaling through ...
Interactions between the opioidergic and dopaminergic systems in the nucleus accumbens (NAcb) play a critical role in mediating cocaine withdrawal-induced effects on cell signaling and behavior. In support of this, increased activation of striatal dopamine-D1 receptors (D1R) results in desensitization of ?-opioid receptor (DOR) signaling through adenylyl ...
Acute challenges with psychostimulants such as amphetamine affect impulsive behavior in both animals and humans. With regard to amphetamine, it is important to unravel how this drug affects impulsivity since it is not only a widely abused recreational drug but also regularly prescribed to ameliorate maladaptive impulsivity. Therefore, we studied the effects of amphetamine in two rat models of ...
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 able to evaluate ...
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 able to evaluate ...
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 ...
Recent studies have shown that deep brain stimulation (DBS) of the nucleus accumbens (NAcc) has an inhibitory effect on drug-seeking behaviors including reinstatement responding for cocaine. The objective of the present study was to expand on these findings by assessing the effects of DBS on behaviors related to alcohol consumption. The specific aim of this study was to ...
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
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 ...
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 experiments were performed in awake, ...
Dopamine injected directly into the caudate--putamen, nucleus accumbens or tuberculum olfactorium of rat brain, following a nialamide pretreatment, caused dose-dependent hyperactivity. The hyperactivity was more intense after injections into the nucleus accumbens, but was limited by the development of stereotyped biting when larger doses of dopamine were ...
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 ...
Dopamine D2 and D3 autoreceptors are located on pre-synaptic terminals and are known to control the release and synthesis of dopamine. Dopamine D3 receptors have a fairly restricted pattern of expression in the mammalian brain. Their localization in the nucleus accumbens core and shell is of particular interest because of their association with the ...
We investigated the roles of the core and shell subfields of the nucleus accumbens (NAc) in drug- or foot-shock-induced reactivation of extinguished conditioned place preference (CPP) in morphine-addicted rats. Rats were given electrolytic lesions to either the core or shell after CPP was established. After surgery, a reduction of CPP ...
The effects of prior treatment with cysteamine, a drug which appears to deplete selectively the neuropeptide somatostatin, on apomorphine-induced stereotypy and amphetamine-induced locomotor activity and conditioned place preferences were investigated. Twelve hours following systemic cysteamine injections apomorphine-induced stereotypy was attenuated and striatal somatostatin levels were reduced ...
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 ...
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 ...
Schizophrenia would result from a defective connectivity between several integrative regions as a consequence of neurodevelopmental failure. Various anomalies reminiscent of early brain development disturbances have been observed in patients' left ventral subiculum of the hippocampus (SUB). Numerous data support the hypothesis of a functional dopaminergic dysregulation in schizophrenia. The common ...
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 adults when choosing ...
Do endocannabinoids (eCBs) participate in long-term synaptic plasticity in the brain? Using pharmacological approaches and genetically altered mice, we show that stimulation of prelimbic cortex afferents at naturally occurring frequencies causes a long-term depression of nucleus accumbens glutamatergic synapses mediated by eCB release and presynaptic CB1 ...
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 ...
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 ...
Relief fits the definition of a reward. Unlike other reward types the pleasantness of relief depends on the violation of a negative expectation, yet this has not been investigated using neuroimaging approaches. We hypothesized that the degree of negative expectation depends on state (dread) and trait (pessimism) sensitivity. Of the brain regions that are involved in mediating ...
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 ...
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 ...
Heterozygous rolling Nagoya (rol/+) mice with a Ca(V)2.1?? mutation show normal Y-maze behavior. Intra-accumbens injection of N-methyl-d-aspartate (NMDA; 0-2.0 ?g/side) induced similar spontaneous alternations in wild-type and rol/+ mice; injections of NMDA receptor antagonist MK-801 (0.5 ?g/side) or Ca(V)2.1 inhibitor levetiracetam (0.1 ?g/side) did not affect controls but ...
Positive social interactions are essential for emotional well-being and proper behavioral development of young individuals. Here, we studied the neural underpinnings of social reward by investigating the involvement of opioid neurotransmission in the nucleus accumbens (NAc) in social play behavior, a highly rewarding social interaction in adolescent rats. Intra-NAc infusion of ...
We have previously shown that acetaldehyde (ACD), the first metabolite of ethanol, regulates its motivational properties and possesses reinforcing effects by itself. A large and still growing body of evidence indicates that the endogenous opioidergic system plays a critical role in the motivational effects of ethanol and suggests a role for extracellular signal-regulated kinase (ERK) in these ...
BackgroundHomer proteins are constituents of scaffolding complexes that regulate the trafficking and function of central Group1 metabotropic glutamate receptors (mGluRs) and N-methyl-D-aspartate (NMDA) receptors. Research supports the involvement of these proteins in ethanol-induced neuroplasticity in mouse. In this study, we examined the effects of short versus long-term withdrawal from chronic ...
There is increasing focus on the role of the nucleus accumbens (NAc) in learning and memory, but there is little consensus as to how the core and medial shell subregions of the NAc contribute to these processes. In the current experiments, we used spontaneous object recognition to test rats with 6-hydroxydopamine lesions targeted at the ...
Neonatal quinpirole treatment to rats produces long-term increases in D(2) receptor sensitivity that persists throughout the animal's lifetime, a phenomenon referred to as D(2) priming. Male and female Sprague-dawley rats were administered quinpirole (1 mg kg(-1)) or saline from postnatal days (P)1-11. At P60, all animals were given an injection of quinpirole (100 microg kg(-1)), and results ...
We previously reported that brief (1 h), but not extended (6 h), daily access to cocaine results in a sensitized locomotor response to cocaine and in elevated c-Fos immunoreactivity and DAT binding in the nucleus accumbens (N.Acc) core. In order to better our understanding of the neural adaptations mediating the transition from ...
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), whereas the ...
BackgroundCalcium/calmodulin-dependent protein kinase IV (CaMKIV) controls activity-dependent gene transcription by regulating the activity of the cyclic AMP response element binding protein (CREB). This signaling pathway is involved in gating emotional responses in the CNS but previous studies did not address the potential roles of CaMKIV in discrete brain regions. In the present study, we aimed ...
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 ...
. The discriminative stimulus effects of ethanol are mediated by NMDA and GABAA receptors in specific limbic brain into the nucleus accumbens substitute for the discriminative stimulus effects of ethanol. Alcohol Clin Exp Res 25 effects of ethanol in mice. Alcoholism Clinical and Experimental Research, 27:1912-1920; 2003. Schroeder
channels; mice Derivatives of Cannabis sativa (L.), such as marijuana and hash- ish, have been used. sativa, ( )-trans-delta9-tetrahydrocannabinol, as well as canna- bimimetics and endocannabinoids, mediate., 1998). Although cannabis derivatives are the most common illicit drugs, little is known
. 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
cannabinoids, such as the active component of Cannabis sativa L, ( )-transdelta9-tetrahydrocannabinol, as well important to the behavioral effects of cannabis use (e.g., the cerebellum, the hippocampus, and the NAc by an exogenous cannabinoid gives insight into how cannabis derivatives such as marijuana alter normal e
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
The core and shell subregions of the nucleus accumbens receive differential projections from areas of the medial prefrontal cortex that have dissociable effects on impulsive and perseverative responding. The contributions of these subregions to simple instrumental behaviour, inhibitory control and behavioural flexibility were investigated using a 'forced ...
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 ...
SummaryThe cellular mechanisms underlying pathological alcohol seeking remain poorly understood. Here, we show an enhancement of nucleus accumbens (NAcb) core action potential firing ex vivo after protracted abstinence from alcohol but not sucrose self-administration. Increased firing is associated with reduced small-conductance calcium-activated potassium ...
There is good evidence that forebrain serotonergic systems modulate cognitive flexibility. Latent inhibition (LI) is a cross-species phenomenon which manifests as poor conditioning to a stimulus that has previously been experienced without consequence and is widely considered an index of the ability to ignore irrelevant stimuli. While much research has focused on dopaminergic mechanisms underlying ...
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 ...
The present investigations sought to determine whether the ventral tegmental area (VTA), basolateral amygdala (BLA), and nucleus accumbens shell (NAC) comprise a circuitry that mediates heroin-induced conditioned immunomodulation. Rats were given conditioning trials in which they received an injection of heroin upon placement into a distinctive ...
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 ...
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 ...
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 dopamine 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 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+ ...
Palatable food intake reduces stress responses, suggesting that individuals may consume such ?comfort? food as self-medication for stress relief. The mechanism by which palatable foods provide stress relief is not known, but likely lies at the intersection of forebrain reward and stress regulatory circuits. Forebrain opioidergic and gamma-aminobutyric acid ergic signaling is critical for both ...
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 ...
Animals recognize a taste cue as aversive when it has been associated with post-ingestive malaise; this associative learning is known as conditioned taste aversion (CTA). When an animal consumes a new taste and no negative consequences follow, it becomes recognized as a safe signal, leading to an increase in its consumption in subsequent presentations (attenuation of neophobia, AN). It has been ...
Prepulse inhibition (PPI) refers to the reduction in the startle response when a startling stimulus is preceded by a weak prestimulus, and is an endophenotype of deficient sensorimotor gating in several neuropsychiatric disorders. Emerging evidence suggests that norepinephrine (NE) regulates PPI, however, the circuitry involved is unknown. We found recently that stimulation of the locus coeruleus ...
Brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, play prominent roles in food intake regulation through central mechanisms. However, the neural circuits underlying their anorexigenic effects remain largely unknown. We showed previously that selective BDNF depletion in the ventromedial hypothalamus (VMH) of mice resulted in hyperphagic behavior and obesity. Here, we sought to ...
During Pavlovian-to-instrumental transfer (PIT), learned Pavlovian cues significantly modulate ongoing instrumental actions. This phenomenon is suggested as a mechanism under which conditioned stimuli may lead to relapse in addicted populations. Following discriminative Pavlovian learning and instrumental conditioning with sucrose, one group of rats (naive) underwent electrophysiological ...
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 reward on a probabilistic ...
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 reward on a probabilistic ...
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 ...
To dissociate a choice from its antecedent neural states, motivation associated with the expected outcome must be captured in the absence of choice. Yet, the neural mechanisms that mediate behavioral idiosyncrasies in motivation, particularly with regard to complex economic preferences, are rarely examined in situations without overt decisions. We employed functional magnetic ...
The stable transcription factor ?FosB is induced in the nucleus accumbens (NAc) by chronic exposure to several drugs of abuse, and transgenic expression of ?FosB in the striatum enhances the rewarding properties of morphine and cocaine. However, the mechanistic basis for these observations is incompletely understood. We used a bitransgenic mouse model with inducible expression ...
... GLU projections from the neo- or allocortex have been found to terminate in nucleus accumbens and other forebrain and hypothalamic nuclei. ...
DTIC Science & Technology
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 clearance times. Following ...
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 ...
The nucleus accumbens (NAc) is involved in many reward-related behaviors. The NAc has two major components, the core and the shell. These two areas have different inputs and outputs, suggesting that they contribute differentially to goal-directed behaviors. Using a discriminative stimulus (DS) task in rats and inactivating the NAc by blocking excitatory ...
Neonatal quinpirole treatment to rats produces long-term increases in D2 receptor sensitivity that persists throughout the animal's lifetime, a phenomenon referred to as D2 priming. Male and female Sprague-dawley rats were administered quinpirole (1mg/kg) or saline from postnatal days (P)1�11. At P60, all animals were given an injection of quinpirole ...
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 (NAc) plays a central role in motivation and reward. While there is ample evidence for sex differences in addiction-related behaviors, little is known about the neuroanatomical substrates that underlie these sexual dimorphisms. We investigated sex differences in synaptic connectivity of the NAc by evaluating pre- and postsynaptic measures in gonadally ...
There is a shift in sensitivity to systemically administered psychostimulants in adolescence, as evidenced by less amphetamine-induced locomotor activity in adolescent compared to adult rodents. Locomotor activating effects of amphetamine are dependent on drug actions in the core of the nucleus accumbens (NAc), but the contribution of this region to age ...
Both the dorsal and ventral striatum have been demonstrated to have a critical role in reinforcement learning and addiction. Dissecting the specific function of these striatal compartments and their associated nigrostriatal and mesoaccumbens dopamine pathways, however, has proved difficult. Previous studies using lesions to isolate the contribution of nigrostriatal and mesoaccumbens dopamine in ...
Here, we characterized behavioral abnormalities induced by prolonged social isolation in adult rodents. Social isolation induced both anxiety- and anhedonia-like symptoms and decreased cAMP response element�binding protein (CREB) activity in the nucleus accumbens shell (NAcSh). All of these abnormalities were reversed by chronic, but not acute, antidepressant treatment. ...
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 ...
In contrast to the vast literature on stress effects on the brain, relatively little is known about the molecular mechanisms of resilience, the ability of some individuals to escape the deleterious effects of stress. Here we show that the transcription factor, ?FosB, mediates an essential mechanism of resilience in mice. Induction of ?FosB in the nucleus ...
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 different conditions ...
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 nucleus ...
Envisaged as a limbic-motor interface, the mammalian nucleus accumbens (Ac) is responsible for motivation, emotionality, and reward mechanisms. As in mammals, Ac of the domestic chick has three subdivisions: the rostral pole (AcR) lying in the rostral part of basal telencephalon, the core (AcC), corresponding to the ventromedial medial striatum, and the ...
BackgroundLong-lasting increases in dendritic spine density and gene expression in the nucleus accumbens and in the ambulatory response to cocaine occur following chronic cocaine treatment. Despite numerous reports of these findings, the molecular mechanisms leading to these morphological, biochemical and behavioral changes remain unclear.MethodsWe used mice genetically ...
Medium-sized spiny projection neurons (MSN) in the head of the primate caudate nucleus are thought to have preferred dendritic orientations that tend to parallel the orientations of the striosomes. Moreover, recurrent axon collaterals of MSN in the rat dorsal striatum have been categorized into two types, i.e., restricted and widespread. The nucleus accumbens (Acb) has a ...
The dopaminergic innervation of the nucleus accumbens (NAc) is implicated in the selection and integration of motivationally relevant corticolimbic information that governs behavioral output. However, it is unknown whether the dopaminergic innervations of two anatomically distinct subregions of the NAc, core and shell, have differential roles in this ...
In our prior studies, systemic administration of the opioid receptor antagonist naltrexone (NTX) did not block flavor preference conditioning by the sweet taste or post-oral actions of sugar despite reducing intake. Because opioid signaling in the nucleus accumbens (NAc) is implicated in food reward, this study determined if NTX administered into the NAc would block the ...
What brain reward systems mediate motivational �wanting� and hedonic �liking� for food rewards? And what roles do those systems play in eating disorders? This article surveys recent findings regarding brain mechanisms of hedonic �liking�, such as the existence of cubic-millimeter hedonic hotspots in nucleus accumbens and ventral pallidum for ...
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 ...
Given the increasing research emphasis on putative accumbal functional compartmentation, we sought to determine whether neurons that demonstrate changes in tonic firing rate during cocaine self-administration are differentially distributed across subregions of the NAcc. Rats were implanted with jugular catheters and microwire arrays targeting NAcc subregions (Core, Dorsal ...
BACKGROUND: Perseveration and sensorimotor gating deficits are core features of obsessive-compulsive disorder (OCD). Serotonin 1B receptor (5-HT1BR) agonists exacerbate OCD symptoms in patients and induce perseveration and sensorimotor gating deficits in mice. Serotonin reuptake inhibitors (SRIs), but not noradrenaline reuptake inhibitors (NRIs), reduce OCD symptoms following ...
There is accumulating evidence that the nucleus accumbens (NAc) plays an important role in the pathophysiology of depression. Given that clinical depression is marked by anhedonia (diminished interest or pleasure), dysfunction of the brain reward pathway has been suggested as contributing to the pathophysiology of depression.Since the NAc is the center of reward and learning, ...
Drug seeking behavior can be reduced or inhibited via extinction. The brain mechanisms for extinction of drug seeking are poorly understood but are of significant interest because of their potential to identify novel approaches that promote abstinence from drug taking. Here we review recent literature on the neural mechanisms for extinction in drug self-administration paradigms. First, we consider ...
Exposure to abused drugs and stressful experience, two factors that promote the development of addiction, also modify synaptic function in the mesolimbic dopamine system. Here, we show that exposure to a novel environment produces functional synaptic adaptations in the nucleus accumbens (NAc) that mirror the effect of conventional forms of stress. We find an enhancement of ...
Caffeine, the most widely used psychoactive compound, is an adenosine receptor antagonist. It promotes wakefulness by blocking adenosine A(2A) receptors (A(2A)Rs) in the brain, but the specific neurons on which caffeine acts to produce arousal have not been identified. Using selective gene deletion strategies based on the Cre/loxP technology in mice and focal RNA interference to silence the ...
The anterior medial prefrontal cortex (aMPFC) is consistently active during personally salient decisions, yet the differential contributory processes of this region along the dorsal�ventral axis are less understood. Using a self-appraisal decision-making task and functional magnetic resonance imaging, we demonstrated task-dependent connectivity of ventral aMPFC with amygdala, insula, and nucleus ...
Figure 4: Effects of pain and placebo on the activation of �µ-opioid receptor-mediated neurotransmission. Legend: Activation of the �µ-opioid system detected by radioligand [11C]carfentanil PET during a tonic pain (A) and placebo analgesia (B). Amy, amygdala; DACing, dorsal anterior cingulate; DLPFC, dorsolateral prefrontal cortex; Ins, insula; MPFC, medial prefrontal ...
BackgroundRegulator of G protein signaling 4 (RGS4) is one of the smaller members of the RGS family of proteins, which are known to control signaling amplitude and duration via interactions with G protein ? subunits or other signaling molecules. Earlier evidence suggests dynamic regulation of RGS4 levels in neuronal networks mediating actions of opiates and other drugs of ...
Synaptic modifications in the nucleus accumbens (NAc) play a key role in adaptive and pathological reward-dependent learning. Medium spiny neurons (MSNs), the major cell type in the NAc, participate in two parallel circuits that subserve distinct behavioral functions yet little is known about differences in their electrophysiological and synaptic properties. Here we utilize ...
Synaptic modifications in the nucleus accumbens (NAc) are important for adaptive and pathological reward-dependent learning. Medium spiny neurons (MSNs), the major cell type in the NAc, participate in two parallel circuits that subserve distinct behavioral functions, yet little is known about differences in their electrophysiological and synaptic properties. Using bacterial ...
Previous work has implicated the cholinergic system in modulating feeding behavior; however its specific function remains unclear. The present work aimed to characterize potential dissociations between the central cholinergic modulation of the incentive properties of food and food-associated cues, versus consummatory behaviors. Three separate experiments demonstrated that ...
Female songbirds display preferences for certain song characteristics, but the neural and hormonal mechanisms mediating these preferences are not fully clear. The present study sought to further explore the role of estradiol, as well as assess potential roles of dopaminergic systems, on behavioral responses to song. Adult female zebra finches were treated with estradiol and ...
The herbicide atrazine (ATR) is widely used around the world, and is a potential toxicant of the dopaminergic systems. Nigrostriatal and mesolimbic systems are the two major dopaminergic pathways of the central nervous system; they play key roles mediating a wide array of critical motor and cognitive functions. We evaluated the effects of exposing male rats for one year to 10 ...
To date, there are no effective pharmacotherapies for treating psychostimulant abuse. Previous preclinical and clinical studies have shown that continuous treatment with the monoamine releaser amphetamine reduces cocaine self-administration, but amphetamine selectively targets the dopamine system and is reinforcing. In the present study, we examined the consequences of administration of ...
BackgroundThe long-term effects of cocaine on behavior are accompanied by structural changes in excitatory glutamatergic synapses onto the medium spiny neurons of the striatum. The Kalrn gene encodes several functionally distinct isoforms; these multidomain guanine nucleotide exchange factors (GEFs) contain additional domains known to interact with phosphatidylinositides as well as with a number ...
The multiprotein Mediator complex has been shown to interact with gene-specific regulatory proteins and RNA polymerase II in vitro. Here, we use chromatin immunoprecipitation to analyze the recruitment of Mediator to GAL genes of yeast in vivo. We find that Mediator associates exclusively with transcriptionally active and not inactive ...
The nucleus accumbens (NA) has been hypothesized to be part of a circuit in which cue-evoked information about expected outcomes is mobilized to guide behavior. Here we tested this hypothesis using a Pavlovian reinforcer devaluation task, previously applied to assess outcome-guided behavior after damage to regions such as the orbitofrontal cortex and amygdala that send ...
Previous findings indicate that the basolateral amygdala (BLA) and the nucleus accumbens (NAc) interact in influencing memory consolidation. The current study investigated whether this interaction requires concurrent dopamine (DA) receptor activation in both brain regions. Unilateral, right-side cannulae were implanted into the BLA and the ipsilateral NAc shell or ...
This study examined the effects of simultaneous variations in motivational state (food deprivation) and reinforcer magnitude (food presentation) on c-Fos immunoreactivity in the pre-and infralimbic medial prefrontal cortex (mPFC), nucleus accumbens (NAcc) core and shell, and dorsal striatum. In the first experiment, c-Fos was reliably increased in pre- and ...
Past reports have shown dopamine (DA) D2/D3 receptor agonist quinpirole (QNP) and the DA D2 receptor antagonist, haloperidol (HAL) display a significant increase in expression of catecholamine regulated protein (CRP40) in the nucleus accumbens (NAcc) and the striatum, respectively. The present study investigated the in vivo effects of QNP and HAL on CRP40 protein levels within ...
Previous studies have shown that the prior administration of metabotropic glutamate receptor 5 (MGluR5) receptor antagonists inhibit responding for nicotine in an intravenous self-administration experiment. However, recent studies in this laboratory have shown that an mGluR5 receptor antagonist, MPEP (2-methyl-6-(phenylethynyl)-pyridine), also attenuates contextually-conditioned responding evoked ...
Neurochemical, electrophysiological and behavioural evidence indicates that certain forms of goal-directed behaviours are mediated by complex and reciprocal interactions between limbic and dopamine (DA) inputs in the nucleus accumbens (NAc). Mesoaccumbens DA transmission appears to be compartmentalized; synaptic DA transmission is ...
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 dopamine neurons make up ...
T-type calcium channels are important in burst firing and expressed in brain regions implicated in schizophrenia. Therefore, we examined the effects of novel selective T-type calcium channel antagonists in preclinical assays predictive of antipsychotic-like activity. TTA-A2 blocked the psychostimulant effects of amphetamine and MK-801 and decreased conditioned avoidance responding. These effects ...
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 increase of the ...
An important issue in affective neuroscience concerns the role of mesocorticolimbic dopamine systems in positive-valenced motivation (e.g., reward) versus negative-valenced motivation (e.g., fear). Here, we assessed whether endogenous dopamine receptor stimulation in nucleus accumbens contributes to both appetitive behavior and fearful behavior that is generated in keyboard ...
The present study reports the first comprehensive map of brain networks underlying latent inhibition learning and the first application of structural equation modeling to cytochrome oxidase data. In latent inhibition, repeated exposure to a stimulus results in a latent form of learning that inhibits subsequent associations with that stimulus. As neuronal energy demand to form learned associations ...
BACKGROUND: Genetic factors and early-life adversity are critical in the etiology of mood disorders and substance abuse. Because of their role in the transduction of stress responses, glucocorticoid hormones and their receptors could serve as both genetic factors and mediators of environmental influences. We have shown that constitutive overexpression of the glucocorticoid ...
Caffeine is the most widely used psychoactive substance and has been considered occasionally as a drug of abuse. The present paper reviews available data on caffeine dependence, tolerance, reinforcement and withdrawal. After sudden caffeine cessation, withdrawal symptoms develop in a small portion of the population but are moderate and transient. Tolerance to caffeine-induced stimulation of ...
BackgroundSensitivity to reward has been implicated as a predisposing factor for behaviors related to drug abuse as well as overeating. However, the underlying mechanisms contributing to reward sensitivity are unknown. We hypothesized that a dysregulation in dopamine signaling might be an underlying cause of heightened reward sensitivity whereby rewarding stimuli could act to normalize the ...
Rat maternal behavior is a complex social behavior. Most antipsychotic drugs disrupt active maternal responses (e.g., pup retrieval, pup licking and nest building). Our previous work shows that typical antipsychotic haloperidol disrupts maternal behavior by blocking dopamine D2 receptors, whereas atypical clozapine works by blocking 5-HT2A/2C ...
The molecular basis underlying hepatitis C virus (HCV) core protein maturation and morphogenesis remains elusive. We characterized the concerted events associated with core protein multimerization and interaction with membranes. Analyses of core proteins expressed from a subgenomic system showed that the signal sequence located between ...
For over 60 years, the Federal Mediation and Conciliation Service (FMCS) has delivered neutral and confidential conflict resolution assistance to the nations unionized workplaces. The core mission of FMCS is to help employers and unions avoid costly work ...
National Technical Information Service (NTIS)
For 60 years, the Federal Mediation and Conciliation Service (FMCS) has delivered neutral and confidential conflict resolution assistance to the nation's unionized workplaces. The core mission of FMCS is to help employers and unions avoid costly work stop...
For more than 60 years, the Federal Mediation and Conciliation Service (FMCS) has delivered neutral and confidential conflict resolution assistance to the nations unionized workplaces. The core mission of FMCS is to help employers and unions avoid costly ...
... Lysine acetylation or Nε-acetylation, identified initially on core histones in 1968 [6], is mediated by a group of enzymes called histone ...
... Abstract : CdSe(sub x)Te(sub 1-x ... and electronic properties of nanoparticles has been ... A structural transformation in the nanoparticle core mediated ...
Magnetic core-shell cylinders comprising a hard dot and a soft ring are proposed. Due to energy redistribution, a compelled vortex is formed on the central dot. Current-driven vortex dynamics is clarified. Because of the confinement effect, the vortex-core gyrotropic motion, and further the vortex-antivortex pair mediated reversal are ...
NASA Astrophysics Data System (ADS)
Methamphetamine (Meth) is a highly addictive stimulant. Meth abuse is commonly associated with the practice of sexual risk behavior and increased prevalence of Human Immunodeficiency Virus and Meth users report heightened sexual desire, arousal, and sexual pleasure. The biological basis for this drug-sex nexus is unknown. The current study demonstrates that Meth administration in male rats ...
Here we define the expression of ?100 transcription factors in progenitors and neurons of the developing basal ganglia. We have begun to elucidate the transcriptional hierarchy of these genes with respect to the Dlx homeodomain genes, which are essential for differentiation of most GABAergic projection neurons of the basal ganglia. This analysis identified Dlx-dependent and Dlx-independent ...
that the mediator, besides forward- ing the synchronization messages between the two protocols (i.e., the onesTowards a Formalization of Mediating Connectors for on the Fly Interoperability Romina Spalazzese.issarny@inria.fr Abstract--Mediators stand as a core architectural paradigm for today's and future systems ...
Human and animal studies indicate that drugs of abuse affect males and females differently, but the mechanism(s) underlying sex differences are unknown. The nucleus accumbens (NAc) is central in the neural circuitry of addiction and medium spiny neurons (MSNs) in the NAc show drug-induced changes in morphology and physiology including increased dendritic spine density. We ...
Neural integration of glutamate- and dopamine-coded signals within the nucleus accumbens (NAc) is a fundamental process governing cellular plasticity underlying reward-related learning. Intra-NAc core blockade of NMDA or D1 receptors in rats impairs instrumental learning (lever-pressing for sugar pellets), but it is not known during which phase of learning ...
