The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior

McFarland, Krista; Kalivas, Peter W.

doi:10.1523/jneurosci.21-21-08655.2001

Cited by 905Neurotransmitter Receptor Influence on BehaviorNeural and Behavioral Psychology StudiesSubstance Abuse Treatment and Outcomes

The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior

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McFarland, Krista, Kalivas, Peter W.·2001·The Journal of Neuroscience

DOI 10.1523/jneurosci.21-21-08655.2001PMC PMC6762812

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Abstract

The role of limbic-striato-pallidal circuitry in cocaine-induced reinstatement was evaluated. The transient inhibition of brain nuclei associated with motor systems [including the ventral tegmental area (VTA), dorsal prefrontal cortex (dPFC), core of the nucleus accumbens (NAcore), and ventral pallidum (VP)] prevented cocaine-induced reinstatement. However, only the VP proved to be necessary for food reinstatement, suggesting that the identified circuit is specific to drug-related reinstatement. Supporting the possibility that the VTA-dPFC-NAcore-VP is a series circuit mediating reinstatement, simultaneous unilateral microinjection of GABA agonists into the dPFC in one hemisphere and into the VP in the contralateral hemisphere abolished cocaine reinstatement. Although dopamine projections from the VTA innervate all three forebrain nuclei, the blockade of dopamine receptors only in the dPFC antagonized cocaine-induced reinstatement. Furthermore, DA administration into the dPFC was sufficient to elicit a reinstatement in drug-related responding. These data demonstrate that dopamine release in the dPFC initiates a dPFC-NAcore-VP series circuit that mediates cocaine-induced drug-seeking behavior.

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Rodent evidence suggests that drug-induced reinstatement is mediated by the circuit linking the prelimbic prefrontal cortex to the ventral striatum.
“Evidence from rodent studies suggests that drug-induced reinstatement is mediated by the circuit that links the prelimbic prefrontal cortex to the ventral striatum94”
From Neurobiology of addiction: a neurocircuitry analysis (2016) · cites this paper as [94]
In cocaine reinstatement models, systemic administration of cocaine reinstates conditioned responding, and this cocaine-induced reinstatement is blocked by administration of dopamine receptor antagonists into the medial shell, but not the core.
“For instance, in animals that have extinguished conditioned responding (lever-pressing), systemic administration of cocaine reinstates the conditioned responding, and this cocaine-induced reinstatement is blocked by the administration of dopamine receptor antagonists into the medial shell, but not the core (McFarland and Kalivas, 2001; Anderson et al., 2003; Bachtell et al., 2005; Anderson et al.,”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as McFarland and Kalivas, 2001

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Authors: McFarland, K., & Kalivas, P. W.
Affiliations: Medical University of South Carolina (US)
ORCID: Kalivas, Peter W.
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2001-11-01
Volume: 21
Issue: 21
Pages: 8655-8663
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.21-21-08655.2001
PMC: PMC6762812
OpenAlex: W1962727914
Semantic Scholar: 471d465e3b760f2c735cb3998066702e05eb0d80
Cited by: 905
References: 54
Citations by year: 2026: 6 · 2025: 20 · 2024: 17 · 2023: 20 · 2022: 23 · 2021: 29 · 2020: 33 · 2019: 39 · 2018: 36 · 2017: 38 · 2016: 52 · 2015: 40 · 2014: 53 · 2013: 59 · 2012: 38
FWCI: 10.56
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Journal of Neuroscience (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: U.S. Public Health Service (DA-12513, DA-03906)
National Institute of Mental Health (R01MH040817, MH-40817)
National Institute on Drug Abuse (DA-05978, R37DA003906, DA-12513, F32DA005978, DA03906, R01DA012513, R01DA003906)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
Health Sciences › Medicine › Epidemiology › Substance Abuse Treatment and Outcomes
Keywords: cocaine, reinstatement of drug seeking, ventral pallidum, dorsal prefrontal cortex, nucleus accumbens core, ventral tegmental area, dopamine, GABA agonists, dopamine receptor blockade, series circuits
MeSH terms: Animals, Behavior, Animal, Chronic Disease, Cocaine, Disease Models, Animal, Dopamine, Globus Pallidus, Injections, Intraperitoneal, Male, Microinjections, Motor Activity, Nerve Net, Nucleus Accumbens, Recurrence, Reinforcement, Psychology, Self Administration, Rats, Sprague-Dawley, Prefrontal Cortex, Ventral Tegmental Area, GABA Agonists, Cocaine-Related Disorders, Rats, GABA-A Receptor Agonists, GABA-B Receptor Agonists

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The circuitry mediating cocaine-induced reinstatement of drug-seeking behavior

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