Tobacco addiction is a serious threat to public health in the United States and abroad, and development of new therapeutic approaches is a major priority. Nicotine, the primary psychoactive compound in cigarette smoke, activates and/or desensitizes nicotinic acetylcholine receptors (nAChRs) throughout the brain. nAChRs in the mesolimbic dopamine (DA) pathway are crucial for the rewarding and reinforcing properties of nicotine in rodent models, suggesting that they may be key mediators of nicotine’s action in humans. Although it is known that a4 and a6 nAChR subunits are important components of mesolimbic DA pathway nAChRs, the precise composition and/or stoichiometry of nAChRs in this pathway that are sufficient and/or necessary for nicotine reward remains unknown. Furthermore, the changes in the brain following nicotine exposure that give rise to reward behavior are poorly understood. This project tests the hypothesis that activation of a4a6b2* nAChRs in the mesolimbic DA pathway is sufficient for nicotine’s rewarding effects. We are using a combination of behavioral, electrophysiological, and biochemical techniques to address this question. These studies will enhance our understanding of the key nAChRs in the mesolimbic DA pathway that are involved in nicotine addiction. Identifying the nAChRs that are sufficient for nicotine reward should lead to a more rational and focused effort to develop new smoking cessation therapeutics.
Publications: 26210579, 25484253, 24266758, 23788655, 23594044, 22885704, 22836257, 22079576, 20660270, 18940593
- NIH K99/R00 DA030396 (PI: Drenan; 2010-2015)
- NIH R01 DA035942 (PI: Drenan; 2014-2019)