Disruption of cocaine self-administration following 6-hydroxydopamine lesions of the ventral tegmental area in rats
Abstract
6-Hydroxydopamine-induced destruction of dopaminergic terminals in the nucleus accumbens have been shown previously to disrupt cocaine and amphetamine self-administration. We sought to determine whether lesions of the DA cell bodies in the ventral tegmental area (VTA) which give rise to the DA innervation of the n. accumbens, would also disrupt cocaine self-administration behavior. Rats were trained to self-inject cocaine (0.75 mg/kg) for 4 hr/day. After a stable baseline was established, one group of rats received bilateral injections of 6-OHDA (4 micrograms/l microliter) into the VTA. Control rats received vehicle injections. When retested on the fifth day post-lesion, all of the 6-OHDA treated animals showed a long lasting reduction in cocaine intake. Three animals did not reinitiate cocaine self-administration after the lesion, although each showed stable post-lesion responding for apomorphine. The surgery had no effect on cocaine self-administration in control animals. These data support the hypothesis that dopaminergic mechanisms are necessary for the normal expression of cocaine self-administration.
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Lesion or inactivation of the mesolimbic DA system in the VTA or NAc decreases cocaine, amphetamine, heroin, and nicotine self-administration in rats.
“In addition, lesion or inactivation of the mesolimbic DA system in the VTA [137,138] or in the NAc [139-143] decreases cocaine, amphetamine, heroin, and nicotine self-administration in rats.”
From Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings (2012) · cites this paper as [137]
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- Authors
- Roberts, D. C. S., & Koob, G. F.
- Affiliations
- Carleton University (CA)
- Salk Institute for Biological Studies (US)
- Venue
- Pharmacology Biochemistry and Behavior
- Publisher
- Elsevier BV
- Published
- 1982-11
- Volume
- 17
- Issue
- 5
- Pages
- 901-904
- ISSN
- 0091-3057 (ISSN-L)
- OpenAlex
- W2077153133
- Cited by
- 448
- References
- 20
- Citations by year
- 2025: 2 · 2024: 1 · 2023: 1 · 2022: 1 · 2021: 5 · 2020: 7 · 2019: 5 · 2018: 8 · 2017: 8 · 2016: 14 · 2015: 8 · 2014: 7 · 2013: 14 · 2012: 9
- FWCI
- 2.25
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacology Biochemistry and Behavior (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
- cocaine self-administration, ventral tegmental area, 6-hydroxydopamine lesion, dopaminergic neurons, nucleus accumbens, dopamine, amphetamine self-administration, apomorphine
- MeSH terms
- Animals, Cocaine, Conditioning, Operant, Dopamine, Hydroxydopamines, Limbic System, Male, Nucleus Accumbens, Rats, Inbred Strains, Receptors, Cholinergic, Receptors, Dopamine, Self Administration, Tegmentum Mesencephali, Oxidopamine, Rats
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