Description:

The Department of Pharmacology is pleased to welcome Dr. Paul J. Kenny, Ph.D.,Ward-Coleman Professor and Chairman of the Arthur M. Fishberg Department of Neuroscience and Director of the Drug Discovery Institute at the Icahn School of Medicine at Mount Sinai.

The following is an overview of this seminar as described by Dr. Kenny:

Relapse rates in tobacco smokers attempting to quit are remarkably high, particularly during the earliest stages of withdrawal when peak craving is experienced, yet little is known about underlying neural mechanisms of relapse in smokers. The septum plays key roles in anxiety, irritability, aggression, memory and reward, processes negatively impacted by withdrawal in smokers. Nevertheless, septal involvement in nicotine craving and relapse has not been explored. We show that chemogenetic stimulation of the triangular nucleus of septum (TNS), but not other septal nuclei, decreases nicotine intake in rats. We show that the TNS provides a major source of excitatory input to the medial habenula, a brain region that controls the motivational properties of nicotine. Moreover, nicotine withdrawal induces profound deficits in septal-derived excitatory transmission in the habenula. Nicotine withdrawal also triggers craving-like responses but only when rats consume quantities of nicotine sufficient to disrupt TNS-derived transmission in the habenula. Chemogenetic stimulation of the TNSàhabenula circuit abolishes withdrawal-induced nicotine craving whereas selective lesion or chemogenetic inhibition of this circuit enhances this craving response. These findings suggest that perturbation of septal communication with the habenula plays a critical role in nicotine craving and relapse.