The smoking cessation medication varenicline attenuates alcohol and nicotine interactions in the rat mesolimbic dopamine system (2009)

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Journal of Pharmacology and Experimental Therapeutics 2009 Jan 6. [Epub ahead of print]

Ericson M, Lof E, Stomberg R, Soderpalm B.

Varenicline was recently approved as an aid for smoking cessation. Patients treated with varenicline have reported a concomitant reduction of their alcohol consumption. This compound has also been demonstrated to reduce alcohol seeking and consumption in alcohol high-preferring rats. Based on the extensive co-abuse of nicotine and alcohol, the aim of the present paper was to explore whether interactions between 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 alcohol, nicotine or the combination of nicotine and alcohol in the experimental rat. Acute systemic co-administration of varenicline and ethanol counteracted each others' respective enhancing effect on dopamine levels in the nucleus accumbens. However, following 5 days of varenicline pre-treatment, acute combined varenicline and ethanol administration raised dopamine levels to the same extent as either drug alone. Furthermore, after varenicline pre-treatment an acute injection of varenicline antagonized the dopamine stimulatory effect of acute nicotine as well as that of systemic co-administration of ethanol and nicotine. In contrast, a pronounced additive dopamine increase was observed when nicotine and ethanol were co-administered in vehicle-pretreated rats. The anti-smoking 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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