M. Imad Damaj, Professor, Pharmacology and Toxicology, Virginia Commonwealth University School of Medicine
Friday December 12, 2014, 10:00 am, Link Auditorium
Mortality from tobacco smoking remains the leading cause of preventable death in the world, yet current cessation therapies are only modestly successful, suggesting new molecular targets are needed. To explore new possibilities, we studied nicotine behavioral effects in the BXD panel of recombinant inbred mouse lines using well established mouse models of reward and withdrawal. We identified a significant correlation between nicotine withdrawal signs and basal galanin or galanin receptor 1 (GALR1) expression in mesolimbocortical dopamine regions across a battery BXD lines. The non-peptide galanin receptor agonist, galnon, reversed precipitated nicotine withdrawal signs in mice. Furthermore, analysis of gene expression and behavior identified in Chrna7 as modulating nicotine conditioned place preference (CPP) in the BXD panel of mice. We used gene targeting and pharmacological tools to confirm its role in nicotine CPP. We found a cis eQTL for Chrna7 in nucleus accumbens that correlated inversely to nicotine CPP. To study molecular events downstream of Chrna7 that may modulate nicotine preference, we performed microarray analysis of α7 KO and WT nucleus accumbens tissue, followed by confirmation with quantitative PCR and immunoblotting. Our genomic studies implicated an mRNA co-expression network regulated by Chrna7 in nucleus accumbens. Mice lacking Chrna7 demonstrate increased insulin signaling in the nucleus accumbens, which may potentially modulate nicotine CPP. Our studies provide novel targets for future work on development of more effective therapeutic approaches for smoking cessation.
Dr. M. Imad Damaj received his Ph.D. from the University of Paris, France in 1991. He did his postdoctoral training at the Department of Pharmacology and Toxicology at Virginia Commonwealth University (VCU) with Dr. Billy R. Martin. Dr. Damaj is currently a Professor of Pharmacology and Toxicology at VCU School of Medicine. His area of research focuses on neuronal mechanisms of pain and the neurobiology of drug addiction, in particular nicotine. He has mentored over 15 Ph.D. and Master students and his research laboratory is funded by the National Institute of Health. He has authored over 155 articles and book chapters in peer review scientific journals and holds several patents.