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Effects of subunit selective nACh receptors on operant ethanol self-administration and relapse-like ethanol-drinking behavior
Department of Clinical Neuroscience, Division of Drug Dependence, Karolinska University Hospital, Stockholm, Sweden.
Institute of Neuroscience and Physiology, Section of Pharmacology, Göteborg University, Göteborg, Sweden.
Department of Clinical Neuroscience, Division of Drug Dependence, Karolinska University Hospital, Stockholm, Sweden.
Institute of Neuroscience and Physiology, Section of Pharmacology, Göteborg University, Göteborg, Sweden.
2009 (English)In: Psychopharmacology, ISSN 0033-3158, E-ISSN 1432-2072, Vol. 203, no 1, 99-108 p.Article in journal (Refereed) Published
Abstract [en]

RATIONALE AND OBJECTIVES: The sensitivity to ethanol central effects is partially determined by the subunit composition of brain nicotinic acetylcholine receptors (nAChRs). Thus, the effects of intraventral tegmental area (VTA) administration of the nicotinic subunit-specific antagonist, alpha-conotoxin MII (alphaCtxMII, alpha(3)beta(2)*, beta(3)*, alpha(6)*), were compared to those of systemic mecamylamine (MEC, an allosteric negative modulator of the nAChR), dihydro-beta-erythroidine (DHbetaE, alpha(4)beta(2)*), and methyllycaconitine (MLA, alpha(7)*) to elucidate involvement of different subunits of nAChRs in operant ethanol self-administration and relapse-like activation of ethanol consumption after ethanol deprivation in rats. METHODS: The effects of drugs were studied in rats trained for operant oral self-administration of ethanol (FR = 1). For ethanol deprivation, trained animals were subjected to a period of alcohol deprivation for 10 days. alphaCtxMII was given directly into the VTA through implanted permanent intracranial cannulae, whereas MEC, DHbetaE, and MLA were administered systemically. RESULTS: alphaCtxMII reduced operant ethanol self-administration and blocked the deprivation-induced relapse-like ethanol consumption. MEC reduced operant ethanol self-administration and inhibited the deprivation-induced increase in alcohol consumption. DHbetaE did not alter ethanol self-administration in the lower-dose range but inhibited ethanol intake at a higher dose (4 mg/kg), although this effect might have been nonspecific. MLA failed to block self-administration of ethanol and relapse-like drinking after deprivation. CONCLUSIONS: Our results indicate that nAChRs are involved in the modulation of operant alcohol self-administration and relapse-like alcohol drinking behavior in rats. Our observations support the working hypothesis that systemically active selective ligands for nAChR alpha(3)beta(2)*, beta(3), and/or alpha(6)* receptor subunits might be of therapeutic value for the treatment of alcoholism.

Place, publisher, year, edition, pages
2009. Vol. 203, no 1, 99-108 p.
Keyword [en]
Ethanol self-administration, Ethanol relapse, Nicotinic AChR subunits, α-conotoxin MII (αCtxMII, α3β2*, β3*, α6*), Mecamylamine Dihydro-β-erythroidine (DHβE, α4β2*), Methyllycaconitine (MLA, α7*)
National Category
Pharmacology and Toxicology Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-120094DOI: 10.1007/s00213-008-1375-5PubMedID: 18987848OAI: oai:DiVA.org:uu-120094DiVA: diva2:302474
Available from: 2010-03-08 Created: 2010-03-07 Last updated: 2017-12-12Bibliographically approved

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