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Combined administration of varenicline and bupropion produces additive effects on accumbal dopamine and abolishes the alcohol deprivation effect in rats

Journal article
Authors Bo Söderpalm
Klara Danielsson
A. de Bejczy
Louise Adermark
Mia Ericson
Published in Addiction Biology
ISSN 1355-6215
Publication year 2019
Published at Institute of Neuroscience and Physiology
Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Language en
Links dx.doi.org/10.1111/adb.12807
Keywords alcohol use disorder, dopamine, ethanol consumption, in vivo microdialysis, nucleus accumbens, rat, nicotinic acetylcholine-receptors, voluntary ethanol intake, ventral, tegmental area, nucleus-accumbens, partial agonist, reinforcing, properties, intake increases, smoking, dependence, placebo, Biochemistry & Molecular Biology, Substance Abuse, tthoff ad, 1983, pharmacology biochemistry and behavior, v18, p489, sner j, 1984, european journal of clinical pharmacology, v26, p627
Subject categories Substance Abuse

Abstract

Alcohol use disorder (AUD) is detrimental to health and causes preterm death. Unfortunately, available pharmacological and nonpharmacological treatments have small effect sizes, and improved treatments are needed. Smoking and AUD share heritability and are pharmacologically associated, since drug-induced dopamine (DA) output in nucleus accumbens (nAc) involves nicotinic acetylcholine receptors (nAChRs) in both cases. Smoking therapy agents, such as the partial nAChR agonist varenicline or the DA/noradrenaline transporter inhibitor bupropion, could potentially also be used for AUD. To investigate this hypothesis, the effects of varenicline, bupropion, or a combination of the two on nAc DA levels, ethanol intake, and the alcohol deprivation effect (ADE) were examined. In vivo microdialysis showed that varenicline (1.5 mg/kg) and bupropion (2.5, 5, or 10 mg/kg) elevated nAc DA levels and that the combination produced additive effects. Five days treatment with varenicline, bupropion, or the combination did not suppress ethanol consumption, as compared with vehicle-treated control. However, combined administration of varenicline and bupropion completely blocked the ADE when readministering ethanol following 14 days of abstinence. Since ADE is considered highly predictive for the clinical outcome in man, our data suggest that the combination of varenicline and bupropion could be a promising treatment for AUD.

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