Anatomical Basis for Nicotine Addiction

Yale University, New Haven CT

Investigators

Linked publications & trials

Abstract

DESCRIPTION (provided by applicant): The primary hypothesis of this proposal is that, in addition to nicotinic acetylcholine receptors (nAChRs) on dopamine neurons, nAChRs on GABA and glutamate neurons in the ventral tegmental area (VTA) shape the response to nicotine in mouse models of addiction. We hypothesize that GABA projection neurons expressing nAChRs contribute to the ability of nicotine to alter responses to environmental cues. Further, we hypothesize that nicotine can stimulate glutamatergic cell bodies in VTA, and that this is essential for the sensitivity to dopamine-dependent behaviors and the long-term responses to nicotine. While acute effects of nicotine are mediated through nAChRs, long-lasting changes in brain circuits and behavior result from downstream effects on intracellular signaling molecules. These signaling molecules are well placed to mediate plastic changes downstream of nAChRs. We will identify the role of signaling molecules co-immunoprecipitated with nAChRs in VTA GABA and glutamate neurons. The specific aims of this proposal are to test the hypothesis that nAChRs on VTA GABA and glutamate neurons are important for the acute and chronic effects of nicotine on circuits and behaviors related to addiction and to identify nAChR-associated signaling molecules in these cell types.