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The persistence of behavioral sensitization to cocaine parallels enhanced inhibition of nucleus accumbens neurons
Open accessAbstract
The mesoaccumbens dopamine system is intricately involved in the locomotor stimulation produced by cocaine and sensitization of this effect following repeated cocaine administration. The mechanisms responsible for the expression of sensitized locomotion appear to involve alterations in both presynaptic (increased dopamine release) and postsynaptic (increased responsiveness of dopamine D1 receptors) aspects of dopamine neurotransmission within the nucleus accumbens. The present experiments used behavioral and single-cell electrophysiological techniques to determine the persistence of sensitization and of enhanced postsynaptic responses to cocaine within the nucleus accumbens following various periods of withdrawal from repeated cocaine treatment (10 mg/kg i.p., twice daily, 14 d). Behavioral sensitization to the locomotor stimulant effects of cocaine was evident after 1 d, 1 week, and 1 month, but not 2 months of withdrawal. A similar time course was observed for the enhanced efficacy of cocaine-induced inhibition of nucleus accumbens neurons, whether cocaine was administered systemically or locally by microiontophoresis. Nucleus accumbens neurons also exhibited sensitized inhibitory responses to iontophoretically applied GABA after 1 d of withdrawal, but not later times. These findings suggest that cocaine sensitization is relatively persistent, but not necessarily permanent, and support the hypothesis that expression of behavioral sensitization to cocaine involves actions within the NAc, particularly those mediated by dopamine D1 receptors.
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“Chronic exposure to cocaine is associated with an increase in phasic D1R signaling, and these increases are involved in reward prediction, sensitized responses to reward, and in dampening further reinforcing effects of drugs of abuse (Ljungberg et al 1992; Henry and White 1995; Self et al 1996; Anderson et al 2008; Bertran-Gonzalez et al 2008; Zweifel et al 2009).”
From The behavioral, anatomical and pharmacological parallels between social attachment, love and addiction (2012) · cites this paper as Henry and White 1995
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Metadata
- Authors
- Henry, D., & White, F.
- Affiliations
- University of Washington (US)
- ORCID
- White, FJ
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 1995-09-01
- Volume
- 15
- Issue
- 9
- Pages
- 6287-6299
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC6577676
- OpenAlex
- W1653336699
- Cited by
- 223
- References
- 23
- Citations by year
- 2026: 1 · 2023: 1 · 2022: 1 · 2021: 1 · 2019: 1 · 2018: 3 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 2 · 2013: 4 · 2012: 4
- FWCI
- 3.60
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k02da000207-04)
- U.S. Public Health Service
- National Institute on Drug Abuse (DA-04093, DA00207)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cognitive Neuroscience › Neural and Behavioral Psychology Studies
- Keywords
- cocaine, behavioral sensitization, nucleus accumbens, dopamine D1 receptor, cocaine withdrawal, locomotor stimulation, postsynaptic inhibition, GABA, microiontophoresis, single-cell electrophysiology
- MeSH terms
- Animals, Behavior, Animal, Cocaine, Electrophysiology, Male, Neural Inhibition, Neurons, Nucleus Accumbens, Time Factors, Rats, Sprague-Dawley, Rats
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