Tobacco addiction is a serious threat to public health, and development of new therapeutic approaches is a major priority. Nicotine 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. We use a variety of approaches to study the specific nAChR subunits and subtypes that mediate cholinergic modulation of DA circuits. A key aspect that we are engaged in is elucidating the identity and function of nAChRs in the various cell types within the midbrain reward system (below). For example, we use Cre/lox methods to identify dopamine-, glutamate-, and GABA-producing neurons in the ventral tegmental area, allowing us to make targeted electrophysiological recordings, image cellular events, and conduct gene expression analyses. We also employ DREADD technology, optogenetics, 2-photon laser scanning microscopy, uncaging techniques, and behavioral methods. Identifying the nAChRs in this pathway will strengthen our understanding of cholinergic control of reward system transmission, and could lead to novel therapeutic approaches for smoking cessation.
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)