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.
Footnotes
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This study was supported by the Swedish Medical Research Council [2006-4988 and 2006-6385], the Swedish Labor Market Insurance (AFA) Support for Biomedical Alcohol Research, the Alcohol Research Council of the Swedish Alcohol Retailing Monopoly, governmental support under the LUA/ALF agreement, Wilhelm and Martina Lundgrens Vetenskapsfond, Fredrik och Ingrid Thurings Stiftelse, Magnus Bergvalls Stiftelse, Gunnar och Märta Bergendahls Stiftelse, Adlerbertska Forskningsfonden, Konrad och Helfrid Johanssons forskningsfond, and Sigurd och Elsa Goljes minne.
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M.E. and E.L. contributed equally to this work.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.108.147058.
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ABBREVIATIONS: nAChR, nicotinic acetylcholine receptor; nAc, nucleus accumbens; VTA, ventral tegmental area; ANOVA, analysis of variance; PLSD, protected least significant difference.
- Received October 17, 2008.
- Accepted January 5, 2009.
- The American Society for Pharmacology and Experimental Therapeutics
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