My overall research goals are centered on elucidating the neurobiological mechanisms underlying motivated behaviors and motivational deficits associated with neuropsychiatric disorders. At present, I am focused on determining how drugs of abuse modulate brain circuitries involved in the emergence and maintenance of drug-seeking behaviors that characterize addiction. While the vast majority of research in the field has focused on the mesocorticolimbic dopamine ‘reward’ pathway, much less is known about the involvement of other motivation-related circuits in addiction. Recently, I established a key role for the medial habenula (MHb) and its major afferent target, the interpeduncular nucleus (IPN), in controlling the addictive properties of nicotine. Specifically, I found that nicotinic acetylcholine receptors (nAChRs) in the MHb-IPN, particularly those containing a5 subunits, control the aversive effects of nicotine and thereby limit consumption of the drug. This finding likely explains why human allelic variation in the gene encoding the a5 subunit gene (CHRNA5) dramatically increases vulnerability to tobacco dependence and smoking-related diseases in humans, such as lung cancer. Moreover, these data have promoted the pharmaceutical development of novel small molecule a5 nAChR ligands that will potentially be used as smoking cessation agents. My lab is currently focused on defining the neurobiological mechanisms in the MHb-IPN circuitry and downstream targets that regulate drug reinforcement, maintenance of drug-seeking behavior, and memory for drug-associated cues.

Drug addiction, nicotine, aversion, genetics, learning, dopamine, motivated behaviors