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Barry J Everitt - One of the best experts on this subject based on the ideXlab platform.
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The basolateral amygdala and Nucleus Accumbens Core mediate dissociable aspects of drug memory reconsolidation.
Learn Mem, 2010Co-Authors: Florence R M Théberge, Amy L Milton, David Belin, Jonathan L C Lee, Barry J EverittAbstract: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 the Nucleus Accumbens Core and the basolateral amygdala in the reconsolidation of a cocaine-conditioned stimulus-evoked memory. Antisense oligodeoxynucleotides (ASO) were infused into each structure to knock down the expression of the immediate-early gene zif268, which is known to be required for memory reconsolidation. Control infusions used missense oligodeoxynucleotides (MSO). The effects of zif268 knockdown were measured in two complementary paradigms widely used to assess the impact of drug-paired CSs upon drug seeking: the acquisition of a new instrumental response with conditioned reinforcement and conditioned place preference. The results show that both intraNucleus Accumbens Core and intrabasolateral amygdala zif268 ASO infusions at memory reactivation impaired the reconsolidation of the memory underlying a cocaine-conditioned place preference. However, knockdown of zif268 in the Nucleus Accumbens at memory reactivation had no effect on the memory underlying the conditioned reinforcing properties of the cocaine-paired CS measured subsequently, and this is in contrast to the marked impairment observed previously following intrabasolateral amygdala zif268 ASO infusions. These results suggest that both the basolateral amygdala and Nucleus Accumbens Core are key structures within limbic cortical-striatal circuitry where reconsolidation of a cue-drug memory occurs. However reconsolidation of memory representations formed during Pavlovian conditioning are differentially localized in each site.
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cocaine seeking habits depend upon dopamine dependent serial connectivity linking the ventral with the dorsal striatum
Neuron, 2008Co-Authors: David Belin, Barry J EverittAbstract:Summary A neuroanatomical principle of striatal organization has been established through which ventral domains, including the Nucleus Accumbens, exert control over dorsal striatal processes mediated by so-called "spiraling," striato-nigro-striatal, circuitry. We have investigated the functional significance of this circuitry in the control over a cocaine-seeking habit by using an intrastriatal disconnection procedure that combined a selective, unilateral lesion of the Nucleus Accumbens Core and infusion of a dopamine receptor antagonist into the contralateral dorsolateral striatum, thereby disrupting striato-midbrain-striatal serial connectivity bilaterally. We show that this disconnection selectively decreased drug-seeking behavior in rats extensively trained under a second-order schedule of cocaine reinforcement. These data thereby define the importance of interactions between ventral and dorsal domains of the striatum, mediated by dopaminergic transmission, in the neural mechanisms underlying the development and performance of cocaine-seeking habits that are a key characteristic of drug addiction.
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differential control over cocaine seeking behavior by Nucleus Accumbens Core and shell
Nature Neuroscience, 2004Co-Authors: Trevor W Robbins, Barry J EverittAbstract:Nucleus Accumbens (NAc) dopamine is widely implicated in mediating the reinforcing effects of drugs of abuse. However, the precise function of the NAc itself in drug self-administration has been difficult to establish. Here we show a neural double-dissociation of the behavioral processes that underlie cocaine self-administration in rats. Whereas selective excitotoxic lesions of the NAc Core had only a minor effect on the acquisition of responding for cocaine under a standard schedule of continuous reinforcement, these lesions profoundly impaired the acquisition of drug-seeking behavior that was maintained by drug-associated conditioned reinforcers and assessed using a second-order schedule of cocaine reinforcement. In contrast, selective excitotoxic lesions of the NAc shell did not impair drug self-administration or the acquisition of cocaine-seeking, but they did attenuate the psychostimulant effects of cocaine. These results further our understanding of how the NAc controls drug-seeking and drug-taking behavior.
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effects of selective excitotoxic lesions of the Nucleus Accumbens Core anterior cingulate cortex and central Nucleus of the amygdala on autoshaping performance in rats
Behavioral Neuroscience, 2002Co-Authors: Rudolf N Cardinal, John A Parkinson, Trevor W Robbins, Guillaume Lachenal, Katherine M Halkerston, Nung Rudarakanchana, Jeremy Hall, Caroline H Morrison, Simon R Howes, Barry J EverittAbstract:The Nucleus Accumbens Core (AcbC), anterior cingulate cortex (ACC), and central Nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.
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impulsive choice induced in rats by lesions of the Nucleus Accumbens Core
Science, 2001Co-Authors: Rudolf N Cardinal, Trevor W Robbins, David R Pennicott, Lakmali C Sugathapala, Barry J EverittAbstract:Impulsive choice is exemplified by choosing a small or poor reward that is available immediately, in preference to a larger but delayed reward. Impulsive choice contributes to drug addiction, attention-deficit/hyperactivity disorder, mania, and personality disorders, but its neuroanatomical basis is unclear. Here, we show that selective lesions of the Nucleus Accumbens Core induce persistent impulsive choice in rats. In contrast, damage to two of its afferents, the anterior cingulate cortex and medial prefrontal cortex, had no effect on this capacity. Thus, dysfunction of the Nucleus Accumbens Core may be a key element in the neuropathology of impulsivity.
Peter W Kalivas - One of the best experts on this subject based on the ideXlab platform.
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n acetylcysteine reverses cocaine induced metaplasticity
Nature Neuroscience, 2009Co-Authors: Khaled Moussawi, Alejandra M Pacchioni, Megan M Moran, Foster M Olive, Justin T Gass, Antonieta Lavin, Peter W KalivasAbstract:The authors report that rats that were withdrawn from cocaine self-administration had an in vivo deficit in their ability to develop long-term potentiation and depression in the Nucleus Accumbens Core following prefrontal cortex stimulation. N-acetylcysteine, a drug that prevents relapse, restored the ability to induce plasticity.
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n acetylcysteine reverses cocaine induced metaplasticity
Nature Neuroscience, 2009Co-Authors: Khaled Moussawi, Alejandra M Pacchioni, Megan M Moran, Foster M Olive, Justin T Gass, Antonieta Lavin, Peter W KalivasAbstract:Cocaine addiction is characterized by an impaired ability to develop adaptive behaviors that can compete with cocaine seeking, implying a deficit in the ability to induce plasticity in cortico-Accumbens circuitry crucial for regulating motivated behavior. We found that rats withdrawn from cocaine self-administration had a marked in vivo deficit in the ability to develop long-term potentiation (LTP) and long-term depression (LTD) in the Nucleus Accumbens Core subregion after stimulation of the prefrontal cortex. N-acetylcysteine (NAC) treatment prevents relapse in animal models and craving in humans by activating cystine-glutamate exchange and thereby stimulating extrasynaptic metabotropic glutamate receptors (mGluR). NAC treatment of rats restored the ability to induce LTP and LTD by indirectly stimulating mGluR2/3 and mGluR5, respectively. Our findings show that cocaine self-administration induces metaplasticity that inhibits further induction of synaptic plasticity, and this impairment can be reversed by NAC, a drug that also prevents relapse.
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glutamate release in the Nucleus Accumbens Core is necessary for heroin seeking
The Journal of Neuroscience, 2008Co-Authors: Ryan T Lalumiere, Peter W KalivasAbstract:Long-term changes in glutamate transmission in the Nucleus Accumbens Core (NACore) contribute to the reinstatement of drug seeking after extinction of cocaine self-administration. Whether similar adaptations in glutamate transmission occur during heroin and cue-induced reinstatement of heroin seeking is unknown. After 2 weeks of heroin self-administration and 2 weeks of subsequent extinction training, heroin seeking was induced by a noncontingent injection of heroin or by presentation of light/tone cues previously paired with heroin infusions. Microdialysis was conducted in the NACore during reinstatement of heroin seeking in animals extinguished from heroin self-administration or in subjects receiving parallel (yoked) noncontingent saline or heroin. Reinstatement by either heroin or cue increased extracellular glutamate in the NACore in the self-administration group, but no increase was elicited during heroin-induced reinstatement in the yoked control groups. The increase in glutamate during heroin-induced drug seeking was abolished by inhibiting synaptic transmission in the NACore with tetrodotoxin or by inhibiting glutamatergic afferents to the NACore from the prelimbic cortex. Supporting critical involvement of glutamate release, heroin seeking induced by cue or heroin was blocked by inhibiting AMPA/kainate glutamate receptors in the NACore. Interestingly, although a heroin-priming injection increased dopamine equally in animals trained to self-administer heroin and in yoked-saline subjects, inhibition of dopamine receptors in the NACore also blocked heroin- and cue-induced drug seeking. Together, these findings show that recruitment of the glutamatergic projection from the prelimbic cortex to NACore is necessary to initiate the reinstatement of heroin seeking.
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ibotenic acid lesions of the dorsal prefrontal cortex disrupt the expression of behavioral sensitization to cocaine
Neuroscience, 1997Co-Authors: R C Pierce, D C Reeder, J Hicks, Z R Morgan, Peter W KalivasAbstract:Abstract The present study determined the effect of bilateral lesions of specific cortical or thalamic nuclei that provide excitatory amino acid afferents to the Nucleus Accumbens (i.e. the dorsal prefrontal cortex, ventral prefrontal cortex, amygdala, hippocampus and periventricular thalamus) on the expression of cocaine-induced behavioral sensitization. Lesions of these nuclei were made during a three-week withdrawal period following repeated daily injections of cocaine or saline. The results indicate that dorsal prefrontal cortex lesions block the expression of behavioral sensitization to cocaine, while ventral prefrontal cortex, fimbria–fornix, amygdala and thalamic lesions have no effect. A subsequent microdialysis experiment was performed in order to evaluate the effect of dorsal prefrontal cortex lesions on glutamate transmission in the Nucleus Accumbens Core of cocaine- and saline-pretreated rats. The systemic injection of cocaine produced a significant increase in extracellular glutamate in the Nucleus Accumbens Core among animals with a sham surgery; this effect was blocked by a bilateral lesion of the dorsal prefrontal cortex. Taken together, these results indicate that the dorsal prefrontal cortex, which provides excitatory amino acid input selectively to the Core region of the Nucleus Accumbens, enhances the expression of behavioral sensitization to cocaine by increasing glutamate transmission in this subNucleus.
Trevor W Robbins - One of the best experts on this subject based on the ideXlab platform.
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differential control over cocaine seeking behavior by Nucleus Accumbens Core and shell
Nature Neuroscience, 2004Co-Authors: Trevor W Robbins, Barry J EverittAbstract:Nucleus Accumbens (NAc) dopamine is widely implicated in mediating the reinforcing effects of drugs of abuse. However, the precise function of the NAc itself in drug self-administration has been difficult to establish. Here we show a neural double-dissociation of the behavioral processes that underlie cocaine self-administration in rats. Whereas selective excitotoxic lesions of the NAc Core had only a minor effect on the acquisition of responding for cocaine under a standard schedule of continuous reinforcement, these lesions profoundly impaired the acquisition of drug-seeking behavior that was maintained by drug-associated conditioned reinforcers and assessed using a second-order schedule of cocaine reinforcement. In contrast, selective excitotoxic lesions of the NAc shell did not impair drug self-administration or the acquisition of cocaine-seeking, but they did attenuate the psychostimulant effects of cocaine. These results further our understanding of how the NAc controls drug-seeking and drug-taking behavior.
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lesions of the medial prefrontal cortex or Nucleus Accumbens Core do not impair inhibitory control in rats performing a stop signal reaction time task
Behavioural Brain Research, 2003Co-Authors: Dawn M Eagle, Trevor W RobbinsAbstract:The 'stop-signal' task measures the ability to inhibit a response that has already been initiated, i.e. the ability to stop. Human subjects who have been classified as 'impulsive', for example, those with attention-deficit/hyperactivity disorder (ADHD), are slower to react to the stop signal, and are often less sensitive to changes in the timing of signals to stop. Imaging studies have implicated fronto-striatal circuitry in the mediation of this form of response control. We report inhibition functions on the stop-signal reaction time (SSRT) task for normal rats, and following damage to the medial prefrontal cortex or to the Nucleus Accumbens Core. Neither group of excitotoxic lesions produced significant deficits on task performance. Subsequent treatment with D-amphetamine (0.3 and 1.0mg/kg) resulted in quicker go-trial reaction times (mRT) overall, but had no significant effect on SSRT. Neither medial prefrontal cortex nor Nucleus Accumbens lesions had any differential effects on performance following D-amphetamine. These results are discussed with respect to the fronto-striatal circuitry involved in the mediation of behavioural inhibition.
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effects of selective excitotoxic lesions of the Nucleus Accumbens Core anterior cingulate cortex and central Nucleus of the amygdala on autoshaping performance in rats
Behavioral Neuroscience, 2002Co-Authors: Rudolf N Cardinal, John A Parkinson, Trevor W Robbins, Guillaume Lachenal, Katherine M Halkerston, Nung Rudarakanchana, Jeremy Hall, Caroline H Morrison, Simon R Howes, Barry J EverittAbstract:The Nucleus Accumbens Core (AcbC), anterior cingulate cortex (ACC), and central Nucleus of the amygdala (CeA) are required for normal acquisition of tasks based on stimulus-reward associations. However, it is not known whether they are involved purely in the learning process or are required for behavioral expression of a learned response. Rats were trained preoperatively on a Pavlovian autoshaping task in which pairing a visual conditioned stimulus (CS+) with food causes subjects to approach the CS+ while not approaching an unpaired stimulus (CS-). Subjects then received lesions of the AcbC, ACC, or CeA before being retested. AcbC lesions severely impaired performance; lesioned subjects approached the CS+ significantly less often than controls, failing to discriminate between the CS+ and CS-. ACC lesions also impaired performance but did not abolish discrimination entirely. CeA lesions had no effect on performance. Thus, the CeA is required for learning, but not expression, of a conditioned approach response, implying that it makes a specific contribution to the learning of stimulus-reward associations.
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impulsive choice induced in rats by lesions of the Nucleus Accumbens Core
Science, 2001Co-Authors: Rudolf N Cardinal, Trevor W Robbins, David R Pennicott, Lakmali C Sugathapala, Barry J EverittAbstract:Impulsive choice is exemplified by choosing a small or poor reward that is available immediately, in preference to a larger but delayed reward. Impulsive choice contributes to drug addiction, attention-deficit/hyperactivity disorder, mania, and personality disorders, but its neuroanatomical basis is unclear. Here, we show that selective lesions of the Nucleus Accumbens Core induce persistent impulsive choice in rats. In contrast, damage to two of its afferents, the anterior cingulate cortex and medial prefrontal cortex, had no effect on this capacity. Thus, dysfunction of the Nucleus Accumbens Core may be a key element in the neuropathology of impulsivity.
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impulsive choice induced in rats by lesions of the Nucleus Accumbens Core but not of anterior cingulate or medial prefrontal cortex
2001Co-Authors: Rudolf N Cardinal, Trevor W Robbins, David R Pennicott, Lakmali C Sugathapala, Barry J EverittAbstract:Impulsive choice is exemplified by the choice of reward that is small, poor, or ultimately disastrous, but is available immediately, in preference to a larger reward obtainable only after a delay. Impulsive choice contributes to neuropsychiatric disorders such as drug addiction as well as attention-deficit/hyperactivity disorder (ADHD), mania, and personality disorders. Impulsive choice hypothetically results from dysfunction of limbic corticostriatal circuitry implicated in reinforcement processes, via convergence on the Nucleus Accumbens. In this first study of the neuro- anatomical basis of impulsive choice, we show that lesions of the Nucleus Accumbens Core (AcbC) induce impulsivity by dramatically and persistently impairing rats' ability to choose a delayed reinforcer. In contrast, lesions of the ante- rior cingulate cortex (ACC) or medial prefrontal cortex (mPFC) had no effect on this capacity, although mPFC lesions appeared to affect general behavioural timing mechanisms. Thus, dysfunction of the AcbC may be a key element in the neuropathology of impulsivity.
John Meitzen - One of the best experts on this subject based on the ideXlab platform.
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estradiol rapidly modulates excitatory synapse properties in a sex and region specific manner in rat Nucleus Accumbens Core and caudate putamen
Journal of Neurophysiology, 2019Co-Authors: Amanda A. Krentzel, Lily R Barrett, John MeitzenAbstract:This study is the first to demonstrate rapid estradiol neuromodulation of glutamatergic signaling on medium spiny neurons (MSNs), the major output neuron of the striatum. These findings emphasize t...
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Biological Sex, Estradiol and Striatal Medium Spiny Neuron Physiology: A Mini-Review
Frontiers in Cellular Neuroscience, 2018Co-Authors: Amanda A. Krentzel, John MeitzenAbstract:The caudate-putamen, Nucleus Accumbens Core and shell are important striatal brain regions for premotor, limbic, habit formation, reward, and other critical cognitive functions. Striatal-relevant behaviors such as anxiety, motor coordination, locomotion, and sensitivity to reward, all change with fluctuations of the menstrual cycle in humans and the estrous cycle in rodents. These fluctuations implicate sex steroid hormones, such as 17β-estradiol, as potent neuromodulatory signals for striatal neuron activity. The medium spiny neuron (MSN), the primary neuron subtype of the striatal regions, expresses membrane estrogen receptors and exhibits sex differences both in intrinsic and synaptic electrophysiological properties. In this mini-review, we first describe sex differences in the electrophysiological properties of the MSNs in prepubertal rats. We then discuss specific examples of how the human menstrual and rat estrous cycles induce differences in striatal-relevant behaviors and neural substrate, including how female rat MSN electrophysiology is influenced by the estrous cycle. We then conclude the mini-review by discussing avenues for future investigation, including possible roles of striatal-localized membrane estrogen receptors and estradiol.
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sex differences in medium spiny neuron excitability and glutamatergic synaptic input heterogeneity across striatal regions and evidence for estradiol dependent sexual differentiation
Frontiers in Endocrinology, 2018Co-Authors: Jinyan Cao, Jaime A Willett, David M Dorris, John MeitzenAbstract:Steroid sex hormones and biological sex influence how the brain regulates motivated behavior, reward, and sensorimotor function in both normal and pathological contexts. Investigations into the underlying neural mechanisms have targeted the striatal brain regions, including the caudate-putamen, Nucleus Accumbens Core and shell. These brain regions are of particular interest to neuroendocrinologists given that they express membrane-associated but not nuclear estrogen receptors, and also the well-established role of the sex steroid hormone 17β-estradiol (estradiol) in modulating striatal dopamine systems. Indeed, output neurons of the striatum, the medium spiny neurons (MSNs), exhibit estradiol sensitivity and sex differences in electrophysiological properties. Here we review sex differences in rat MSN glutamatergic synaptic input and intrinsic excitability across striatal regions, including evidence for estradiol-mediated sexual differentiation in the Nucleus Accumbens Core. In prepubertal animals, female MSNs in the caudate-putamen exhibit a greater intrinsic excitability relative to male MSNs, but no sex differences are detected in excitatory synaptic input. Alternatively, female MSNs in the Nucleus Accumbens Core exhibit increased excitatory synaptic input relative to male MSNs, but no sex differences in intrinsic excitability were detected. Increased excitatory synaptic input onto female MSNs in the Nucleus Accumbens Core is abolished after masculinizing estradiol or testosterone exposure during the neonatal critical period. No sex differences are detected in MSNs in prepubertal Nucleus Accumbens shell. Thus, despite possessing the same neuron type, striatal regions exhibit heterogeneity in sex differences in MSN electrophysiological properties, which likely contribute to the sex differences observed in striatal function.
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Nucleus Accumbens Core medium spiny neuron electrophysiological properties and partner preference behavior in the adult male prairie vole microtus ochrogaster
Journal of Neurophysiology, 2018Co-Authors: Jaime A Willett, Ashlyn G Johnson, Andrea R Vogel, Heather B Patisaul, Lisa A Mcgraw, John MeitzenAbstract:This research represents the first assessment of prairie vole Nucleus Accumbens Core medium spiny neuron intrinsic electrophysiological properties and probes the relationship between cellular excit...
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neonatal masculinization blocks increased excitatory synaptic input in female rat Nucleus Accumbens Core
Endocrinology, 2016Co-Authors: David M Dorris, John MeitzenAbstract:Steroid sex hormones and genetic sex regulate the phenotypes of motivated behaviors and relevant disorders. Most studies seeking to elucidate the underlying neuroendocrine mechanisms have focused on how 17β-estradiol modulates the role of dopamine in striatal brain regions, which express membrane-associated estrogen receptors. Dopamine action is an important component of striatal function, but excitatory synaptic neurotransmission has also emerged as a key striatal substrate and target of estradiol action. Here, we focus on excitatory synaptic input onto medium spiny neurons (MSNs) in the striatal region Nucleus Accumbens Core (AcbC). In adult AcbC, miniature excitatory postsynaptic current (mEPSC) frequency is increased in female compared with male MSNs. We tested whether increased mEPSC frequency in female MSNs exists before puberty, whether this increased excitability is due to the absence of estradiol or testosterone during the early developmental critical period, and whether it is accompanied by stab...
Patricia H Janak - One of the best experts on this subject based on the ideXlab platform.
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long lasting contribution of dopamine in the Nucleus Accumbens Core but not dorsal lateral striatum to sign tracking
European Journal of Neuroscience, 2017Co-Authors: Kurt M Fraser, Patricia H JanakAbstract:The attribution of incentive salience to reward-paired cues is dependent on dopamine release in the Nucleus Accumbens Core. These dopamine signals conform to traditional reward-prediction error signals and have been shown to diminish with time. Here we examined if the diminishing dopamine signal in the Nucleus Accumbens Core has functional implications for the expression of sign-tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward-paired cues. Food-restricted male Sprague-Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol, or the GABA agonists baclofen and muscimol into the Nucleus Accumbens Core or the dorsal lateral striatum. Dopamine antagonism within the Nucleus Accumbens Core attenuated sign-tracking, whereas reversible inactivation did not affect sign-tracking but increased non-specific food cup checking behaviors. Neither drug in the dorsal lateral striatum affected sign-tracking behavior. Critically, extended training did not alter these effects. Though extended experience with an incentive stimulus may reduce cue-evoked dopamine in the Nucleus Accumbens Core, this does not remove the dependence on dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training. This article is protected by copyright. All rights reserved.
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long lasting contribution of dopamine in the Nucleus Accumbens Core but not dorsal lateral striatum to sign tracking
bioRxiv, 2017Co-Authors: Kurt M Fraser, Patricia H JanakAbstract:The attribution of incentive salience to reward-paired cues is dependent on dopamine release in the Nucleus Accumbens Core. These dopamine signals conform to traditional reward-prediction error signals and have been shown to diminish with time. Here we examined if the diminishing dopamine signal in the Nucleus Accumbens Core has functional implications for the expression of sign-tracking, a Pavlovian conditioned response indicative of the attribution of incentive salience to reward-paired cues. Food-restricted male Sprague-Dawley rats were trained in a Pavlovian paradigm in which an insertable lever predicted delivery of food reward in a nearby food cup. After 7 or 14 training sessions, rats received infusions of saline, the dopamine antagonist flupenthixol (100 mM), or the GABA agonists baclofen and muscimol (0.5 mM baclofen/0.05 mM muscimol) into the Nucleus Accumbens Core or the dorsal lateral striatum. Dopamine antagonism within the Nucleus Accumbens Core attenuated sign-tracking, whereas reversible inactivation did not affect sign-tracking but increased non-specific food cup checking behaviors. Neither drug in the dorsal lateral striatum affected sign-tracking behavior. Critically, extended training did not alter these effects. Though extended experience with an incentive stimulus may reduce cue-evoked dopamine in the Nucleus Accumbens Core, this does not alter the function of dopamine in this region to promote Pavlovian cue approach nor result in the recruitment of dorsal lateral striatal systems for this behavior. These data support the notion that dopamine within the mesoaccumbal system, but not the nigrostriatal system, contributes critically to incentive motivational processes independent of the length of training.
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dissociable roles of the medial prefrontal cortex and Nucleus Accumbens Core in goal directed actions for differential reward magnitude
Cerebral Cortex, 2010Co-Authors: Michael T Gill, Paulo J Castaneda, Patricia H JanakAbstract:The medial prefrontal cortex (mPFC) and Nucleus Accumbens (NAc) are 2 structures within a larger corticolimbic network mediating goal-directed actions, especially when the procurement of different goals is sensitive to impulsive tendencies. The present study investigated the role of these structures in goal-directed action for differential reward by training rats to respond for sucrose reward at a nosepoke operandum such that longer duration nosepokes (up to 2 s) resulted in correspondingly larger volumes of reward. After 16 weeks of training, neurotoxic lesions of either the mPFC or the NAc-Core were performed, followed by reassessment of sustained response behavior. Lesions of mPFC increased choice impulsivity by shifting responding away from large rewards toward rewards of smaller sizes. The total volume of reward earned remained unchanged, thereby dissociating the lesion effects on response parameters from overall motivation for reward. In contrast, NAc-Core lesions decreased the total amount of responding and total volume of reward earned without altering choice impulsivity across differing nosepoke durations and reward sizes. These results suggest that the mPFC mediates the ability to maintain behavioral responding over longer durations for larger magnitude rewards, while the NAc-Core mediates the initiation of responding, perhaps by affecting motivational drive, independent of reward magnitude.
