Contribution of dihydro-beta-erythroidine sensitive nicotinic acetylcholine receptors in the ventral tegmental area to cocaine-induced behavioral sensitization in rats
Abstract
Nicotinic acetylcholine receptors (nAChRs) are known to play a role in several aspects of cocaine addiction. Recently, systemic administration of the nicotinic receptor antagonist mecamylamine was shown to block the induction of long-term locomotor sensitization to cocaine. Behavioral sensitization being a model of long-term neuroadaptations to chronic cocaine exposure, the goal of the current study was to identify the anatomical localization, as well as the nature, of the nicotinic receptors involved. Male Sprague-Dawley rats were stereotaxically implanted with bilateral cannula into either the ventral tegmental area (VTA) or the nucleus accumbens (Nacc). On each of the six consecutive days, rats were microinjected bilaterally with the selective nicotinic antagonists dihydro-beta-erythroidine (DHbetaE), methyllycaconitine (MLA) or saline, followed by an intra-peritoneal injection of cocaine (15 mg/kg, i.p.) or saline. Following a 2-week withdrawal period, rats received a final injection of cocaine in the absence of nicotinic antagonist to test for sensitization. When microinjected into the VTA, DHbetaE, but not MLA, prevented the induction of behavioral sensitization to cocaine. In contrast, behavioral sensitization was present in rats receiving DHbetaE microinjections into the Nacc. Neither antagonist, whether injected into the VTA or the Nacc had any significant effect on the acute locomotor response to cocaine. Given the subtype selectivity of the nicotinic antagonists employed, heteromeric beta2-containing (beta2*) nAChRs, but not homomeric alpha7* nAChRs, in the VTA may be involved in the neuroadaptive changes underlying cocaine sensitization.
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Disruption of PPTg activity decreases the rewarding and locomotor effects of drugs of abuse such as cocaine and nicotine.
“At the behavioral level, this conclusion is consistent with the finding that disruption of PPTg activity decreases the rewarding and locomotor effects of drugs of abuse such as cocaine and nicotine (Champtiaux et al., 2006; Corrigall et al., 1994; Corrigall et al., 2002), while lesion of NAc cholinergic neurons increases cocaine self-administration, as might be expected if a pause in cholinergic”
From Acetylcholine as a Neuromodulator: Cholinergic Signaling Shapes Nervous System Function and Behavior (2012) · cites this paper as Champtiaux et al., 2006
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BackgroundResultInfluentialInhibitory influence of mecamylamine on ethanol withdrawal-induced symptoms in C57BL/6J mice
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- Authors
- Champtiaux, N., Kalivas, P. W., & Bardo, M. T.
- Affiliations
- Medical University of South Carolina (US)
- University of Kentucky (US)
- Corresponding author
- Bardo, M.T.
- Venue
- Behavioural Brain Research
- Publisher
- Elsevier BV
- Published
- 2006-03
- Volume
- 168
- Issue
- 1
- Pages
- 120-126
- ISSN
- 0166-4328 (ISSN-L)
- OpenAlex
- W2136149147
- Cited by
- 33
- References
- 53
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2021: 1 · 2019: 4 · 2018: 1 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 4 · 2012: 3
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Behavioural Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Philip Morris International
- National Institutes of Health
- National Institute on Drug Abuse (U19DA017548, DA05312, DA 17548)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Physiology › Smoking Behavior and Cessation
- Keywords
- nicotinic acetylcholine receptors, dihydro-beta-erythroidine, cocaine, behavioral sensitization, ventral tegmental area, nucleus accumbens, mecamylamine, methyllycaconitine, locomotor sensitization, alpha7 nAChR, cocaine dependence, neural adaptation
- MeSH terms
- Aconitine, Animals, Behavior, Animal, Cocaine, Dihydro-beta-Erythroidine, Male, Microinjections, Receptors, Nicotinic, Stereotaxic Techniques, Stereotyped Behavior, Rats, Sprague-Dawley, Ventral Tegmental Area, Nicotinic Antagonists, Rats, alpha7 Nicotinic Acetylcholine Receptor
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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