Differential control over cocaine-seeking behavior by nucleus accumbens core and shell
Abstract
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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Excitotoxic lesions of the core enhance locomotor activity induced by systemic amphetamine or cocaine, suggesting an inhibitory role of the core in psychomotor stimulant-induced locomotion.
“On the other hand, excitotoxic lesions of the core enhance locomotor activity induced by systemic amphetamine or cocaine (Parkinson et al., 1999; Ito et al., 2004), suggesting an inhibitory role of the core in psychomotor stimulant-induced locomotion.”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ito et al., 2004
Core lesions do disrupt instrumental performance that is maintained by the presentation of cocaine-paired conditioned stimuli.
“In any case, the core lesions do disrupt instrumental performance that is maintained by the presentation of cocaine-paired conditioned stimuli (Ito et al., 2004).”
From Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complex (2007) · cites this paper as Ito et al., 2004
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- Authors
- Ito, R., Robbins, T. W., & Everitt, B. J.
- Affiliations
- University of Cambridge (GB)
- Corresponding author
- Everitt, Barry J
- Venue
- Nature Neuroscience
- Published
- 2004-03-21
- Volume
- 7
- Issue
- 4
- Pages
- 389-397
- ISSN
- 1097-6256 (ISSN-L)
- 1546-1726
- OpenAlex
- W2014459415
- Cited by
- 501
- References
- 50
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 12 · 2023: 15 · 2022: 10 · 2021: 21 · 2020: 20 · 2019: 17 · 2018: 14 · 2017: 25 · 2016: 20 · 2015: 18 · 2014: 30 · 2013: 31 · 2012: 34
- FWCI
- 10.30
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- nucleus accumbens, nucleus accumbens core, nucleus accumbens shell, cocaine self-administration, cocaine-seeking behavior, second-order schedules, excitotoxic lesions, drug reinforcement, double dissociation
- MeSH terms
- Animals, Appetitive Behavior, Association Learning, Cocaine, Disease Models, Animal, Dose-Response Relationship, Drug, Male, Nucleus Accumbens, Rats, Inbred Strains, Reinforcement, Psychology, Self Administration, Cocaine-Related Disorders, Rats
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