Northwestern University Feinberg School of Medicine

Ryan Drenan Lab

Nicotine Withdrawal Mechanisms

There is a significant unmet need for more effective strategies to treat cxnicotine dependence. Nicotine exposure produces physical dependence, and the physical and/or emotional nicotine withdrawal symptoms – as compared to the rewarding effects of nicotine – are often the most important contributors to relapse. Unfortunately, a critical gap in knowledge exists regarding our understanding of how chronic nicotine exposure establishes physical dependence and therefore makes smokers highly susceptible to relapse. In this project, we use mouse models to study the medial habenula (MHB), a small brain area in the epithalamic regionthat has recently been implicated in nicotine withdrawal, and which expresses extraordinarily high levels of several types of nicotinic acetylcholine receptors (nAChRs). At right, β4-GFP nAChRs are shown in the medial habenula and in axons of the fasciculus retroflexus. This image was taken from a knock-in mouse expressing GFP-tagged receptors. We are identifying the relevant nAChRs and MHB circuits involved in nicotine dependence and withdrawal. This study will help us solve the problem of understanding how cessation of nicotine intake causes the brain to generate aversive physical and emotional withdrawal responses that inevitably lead to relapse. 

Publications: 26429939, 25031416, 24378908