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The smoking cessation medication varenicline attenuates alcohol and nicotine interactions in the rat mesolimbic dopamine system.

Journal article
Authors Mia Ericson
Elin Löf
Rosita Stomberg
Bo Söderpalm
Published in The Journal of pharmacology and experimental therapeutics
Volume 329
Issue 1
Pages 225-30
ISSN 1521-0103
Publication year 2009
Published at Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry
Pages 225-30
Language en
Links dx.doi.org/10.1124/jpet.108.147058
Keywords Animals, Benzazepines, administration & dosage, pharmacology, Central Nervous System Depressants, pharmacology, Dopamine, metabolism, physiology, Dose-Response Relationship, Drug, Drug Interactions, Ethanol, pharmacology, Limbic System, drug effects, metabolism, Male, Microdialysis, Nicotine, pharmacology, Nucleus Accumbens, drug effects, Quinoxalines, administration & dosage, pharmacology, Rats, Rats, Wistar, Smoking Cessation
Subject categories Pharmacology, Substance Abuse

Abstract

Varenicline was recently approved as an aid for smoking cessation. Patients treated with varenicline have reported a concomitant reduction in their alcohol consumption. This compound has also been demonstrated to reduce alcohol seeking and consumption in alcohol high-preferring rats. Based on the extensive coabuse of nicotine and alcohol, the aim of the present study was to explore whether interactions among varenicline, nicotine, and ethanol in the brain reward system could indicate the use of varenicline also for alcohol dependence. Using the in vivo microdialysis method, we investigated the effects of systemic injections of varenicline on the extracellular accumbal dopamine levels in response to a systemic challenge of ethanol, nicotine, or the combination of nicotine and ethanol in the experimental rat. Acute systemic coadministration of varenicline and ethanol counteracted each others' respective enhancing effect on dopamine levels in the nucleus accumbens. However, after 5 days of varenicline pretreatment, acute combined varenicline and ethanol administration raised dopamine levels to the same extent as either drug alone. Furthermore, after varenicline pretreatment an acute injection of varenicline antagonized the dopamine stimulatory effect of acute nicotine as well as that of systemic coadministration of ethanol and nicotine. In contrast, a pronounced additive dopamine increase was observed when nicotine and ethanol were coadministered in vehicle-pretreated rats. The antismoking agent varenicline exhibits properties with respect to its interaction with ethanol and nicotine in the brain reward system that may be beneficial for treating patients with alcohol dependence with (and possibly also without) concomitant nicotine dependence.

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