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Glycine Receptors Involved in Acamprosate's Modulation of Accumbal Dopamine Levels: An In Vivo Microdialysis Study.

Journal article
Authors Pei Pei Chau
Rosita Stomberg
Anne Fagerberg
Bo Söderpalm
Mia Ericson
Published in Alcoholism, clinical and experimental research
ISSN 1530-0277
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Links dx.doi.org/10.1111/j.1530-0277.2009...
Subject categories Pharmacology, Substance Abuse

Abstract

Background: Glycine receptors (GlyRs) in the nucleus accumbens (nAc) and nicotinic acetylcholine receptors (nAChRs) in the ventral tegmental area (VTA) have been suggested to be involved in the positive reinforcing and dopamine elevating effects of ethanol. Recent studies have also shown that ethanol high-preferring rats substantially decrease their ethanol intake when treated with a glycine transporter 1 inhibitor (ORG 25935). Acamprosate, a drug used for relapse prevention in treatment of alcohol dependence, has also been demonstrated to elevate extracellular dopamine levels in the nAc. However, the underlying mechanism of action of acamprosate is not fully understood. Here we investigated whether acamprosate interferes with a neuronal circuitry that previously has been demonstrated to be involved in the dopamine elevating effects of ethanol and taurine. Methods: In vivo microdialysis in freely moving rats was used to assess accumbal dopamine levels before and during local (nAc) or systemic administration of acamprosate. Results: Perfusion of 0.5 mM acamprosate in the nAc significantly increased dopamine levels. Pretreatment either with 10 muM strychnine in the nAc or 100 muM mecamylamine in the VTA, completely antagonized the acamprosate-induced elevation of accumbal dopamine levels. Also, systemic acamprosate administration elevated accumbal dopamine output, an effect that was abolished by local (nAc) pretreatment with 10 muM strychnine. Conclusions: These results suggest that both systemic and local application of acamprosate elevate extracellular dopamine levels in the nAc by activating accumbal GlyRs, and, secondarily, tegmental nAChRs.

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