Cocaine-Associated Stimuli Increase Cocaine Seeking and Activate Accumbens Core Neurons after Abstinence

Hollander, Jonathan A.; Carelli, Regina M.

doi:10.1523/jneurosci.3667-06.2007

Cited by 135 publications

(143 citation statements)

References 31 publications

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“…In a subsequent study, we also showed that NAc core neurons are more responsive to cocaineassociated cues following 1-month abstinence (Hollander and Carelli, 2007). In this study, animals were trained to self-administer cocaine then returned to their home cages without cocaine access for either 1 day or 1 month.…”

Section: Cocaine Abstinence Alters Nac Cell Firingmentioning

confidence: 70%

Dissecting motivational circuitry to understand substance abuse

Wheeler

Carelli

2009

Neuropharmacology

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SummaryAn important goal of cocaine addiction research is to understand the neurobiological mechanisms underlying this disease state. Here, we review studies from our laboratory that examined nucleus accumbens (NAc) cell firing and rapid dopamine signaling using electrophysiological and electrochemical recordings in behaving rodents. A major advantage of these techniques is that they allow for the characterization of NAc activity and rapid dopamine release during specific phases of motivated behavior. Moreover, each approach enables an examination of the dynamic nature of NAc signaling as a function of factors such as hedonics and associative learning. We show that NAc neurons differentially respond to rewarding and aversive stimuli and their predictors in a bivalent manner. This differential responding is modifiable and can be altered by the presentation of other natural rewards or cocaine. Likewise, the dynamic nature of NAc cell firing is also reflected in the differential activation of distinct populations of NAc neurons during goal-directed behaviors for natural versus drug rewards, and the heightened activation of some NAc neurons following cocaine abstinence. Our electrochemical data also show that rapid dopamine signaling in the NAc reflects primary rewards and their predictors and appears to modulate specific NAc neuronal responses. In some cases, these influences are observed in a regionally specific manner that matches previous pharmacological manipulations. Collectively, these findings provide critical insight into the functional organization of the NAc that can be used to guide additional studies aimed at dissecting the neural code underlying compulsive drug-seeking behavior.

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Section: Cocaine Abstinence Alters Nac Cell Firingmentioning

confidence: 70%

Dissecting motivational circuitry to understand substance abuse

Wheeler

Carelli

2009

Neuropharmacology

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“…Accordingly, we have shown that, in RHA rats sensitized to cocaine, the increment in dopamine efflux elicited by the administration of a cocaine challenge after 1 week of abstinence is potentiated in the NAc-core and concomitantly attenuated in the NAc-shell, whereas such adaptive changes are not observed in sensitization-resistant RLA rats (Giorgi et al, 2007). Importantly, the NAc-core has been implicated in the reinstatement of cocaine-seeking induced by the administration of a priming dose of the drug or by exposure to drug-related cues (Ito et al, 2004;Hollander and Carelli, 2007). These findings support the view that the NAc-core and its afferent glutamatergic projections originating in the mPFC play a key role in cocaine-induced relapse (McFarland et al, 2003).…”

Section: Figurementioning

confidence: 99%

“…It has been proposed that these neural circuits encode and associate information about a primary reinforcer like cocaine with motivated behavior and/or environmental stimuli (Everitt and Wolf, 2002;Schultz, 2002;Hollander and Carelli, 2007). Adaptive changes in this neural circuitry are also believed to underlie the long-term increment in the locomotor activation of rodents (ie, behavioral sensitization) elicited by the repeated exposure to cocaine (Vanderschuren and Kalivas, 2000;Nestler, 2001;Li et al, 2004;Vezina, 2004).…”

Section: Introductionmentioning

confidence: 99%

The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration

Fattore

Piras

Corda

et al. 2008

Neuropsychopharmacol

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The selective breeding of Roman high-(RHA) and low-avoidance (RLA) rats for, respectively, rapid vs extremely poor acquisition of avoidant behavior in a shuttlebox has produced two phenotypes that differ in temperament traits, in mesocortical/mesolimbic dopamine system function, and in the behavioral and neurochemical responses to the acute and repeated administration of psychostimulants and opiates. The phenotypic traits of the RHA line predict higher susceptibility, compared with RLA rats, to the reinforcing properties of addictive substances like cocaine. The present study was designed to compare the acquisition, maintenance, reinstatement of drugseeking after long-term extinction, and reacquisition of intravenous cocaine self-administration (SA) behavior in the Roman lines. Compared with RLA rats, the rates of responding during cocaine SA acquisition were higher, extinction from cocaine SA was prolonged, and drug-induced reinstatement of cocaine-seeking behavior was more robust in RHA rats. Moreover, only RHA rats reacquired extinguished lever-pressing activity when a low reinforcing dose of cocaine was available. These findings are consistent with the view that subjects with genetically determined high responsiveness to the acute and chronic (ie, sensitizing) effects of psychostimulants, such as RHA rats, also display a higher propensity to self -administer cocaine. Further comparative studies in the Roman lines, using SA paradigms that distinguish mere drug-taking from the compulsive and uncontrolled drug use that characterizes addiction in humans, may eventually help to characterize the relationships among genotype, temperament traits, and neurobiological mechanisms involved in the individual vulnerability to cocaine addiction.

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“…Supporting their critical roles in the neural circuitry of drug-seeking behavior, these regions have also been identified using preclinical reinstatement models (8,9). For example, NAc neurons exhibit conditioned responses to drugassociated environmental stimuli even after prolonged drug abstinence, suggesting persistent alterations in reward-related information processing (10), whereas inactivation of the dorsal prefrontal cortex (PFC) or basolateral amygdala blocks cue-induced reinstatement (11).…”

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confidence: 99%

Dorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues

Liu

Chefer

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Chronic drug administration induces neuroplastic changes within brain circuits regulating cognitive control and/or emotions. Following repeated pairings between drug intake and environmental cues, increased sensitivity to or salience of these contextual cues provoke conscious or unconscious craving and enhance susceptibility to relapse. To explore brain circuits participating in such experienceinduced plasticity, we combined functional MRI with a preclinical drug vs. food self-administration (SA) withdrawal model. Specifically, two groups of rats were trained to associate odor cues with the availability of i.v. cocaine or oral sucrose, respectively. After 20 d of cocaine or sucrose SA followed by prolonged (30 d) forced abstinence, animals were presented with odor cues previously associated with or without (S+/S−) reinforcer (cocaine/sucrose) availability while undergoing functional MRI scans. ANOVA results demonstrate that a learning effect distinguishing S+ from S− was seen in the insula and nucleus accumbens, with the insula response reflecting the individual history of cocaine SA intake. A main effect of group, distinguishing cocaine from sucrose, was seen in the medial prefrontal cortex (infralimbic, prelimbic, and cingulate cortex) and dorsolateral striatum. Critically, only the dorsomedial striatum demonstrated a double dissociation between the two SA groups and learning (S+ vs. S−). These findings demonstrate altered cortico-limbic-striatal reward-related processing to learned, environment reward-associated contextual odor cues, which may serve as potential biomarkers for therapeutic interventions.context cues | neuroplasticity | drug addiction P reventing or reducing the incidence of relapse remains the major challenge for the treatment of addiction, as recidivism rates can range as high as 90%. Both preclinical (1) and human addiction studies (2) have demonstrated that following repeated pairings with drug administration, various contextual and environmental stimuli when subsequently presented alone can elicit drug-seeking and drug-taking behaviors. Further, dysregulation within specific brain circuits regulating cognitive control and/or emotional regulation (3) can amplify the perceived salience of environmental contexts and cues that provoke craving (4) and thereby enhance susceptibility to relapse (2). These observations speak to the important role of reward learning in addictive processes (5). As such, it is critical to better understand the neural mechanisms and circuitry underlying the retrieval of cue-induced memories as an important intermediary in developing more efficacious interventions to decrease recidivism.The amygdala, nucleus accumbens (NAc), and various prefrontal cortical regions respond to drug-associated cues in human cocaine addicts (6, 7). Supporting their critical roles in the neural circuitry of drug-seeking behavior, these regions have also been identified using preclinical reinstatement models (8, 9). For example, NAc neurons exhibit conditioned responses to drugassociated env...

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Cocaine-Associated Stimuli Increase Cocaine Seeking and Activate Accumbens Core Neurons after Abstinence

Cited by 135 publications

References 31 publications

Dissecting motivational circuitry to understand substance abuse

Dissecting motivational circuitry to understand substance abuse

The Roman High- and Low-Avoidance Rat Lines Differ in the Acquisition, Maintenance, Extinction, and Reinstatement of Intravenous Cocaine Self-Administration

Dorsolateral caudate nucleus differentiates cocaine from natural reward-associated contextual cues

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