Project Summary

Raad Nashmi, Ph.D. (Young Investigator 2006) of the California Institute of Technology, will conduct an animal model study of a particular subunit of the nicotinic acetylcholine receptor (nAChR) and its role in tobacco addiction. To understand the physiology of nicotinic receptor neurotransmission and its pathophysiology in nicotine addiction, it is essential to have accurate and quantitative information of the subcellular distribution of nAChRs. nAChRs in smokers’ brains are exposed to nicotine for long durations, resulting in increased nicotine binding sites. Does this increased nicotine binding correspond to increased nAChR protein expression and/or receptor assembly? If so, where in the brain does it occur and what specific subtypes of nicotinic receptors contribute to increased nicotine binding? Dr. Nashmi has generated knockin mice with fluorescently labeled α4 nAChR subunits to quantify the neuronal distribution of α4 nAChR subunits at submicron resolution. With these mice, Dr. Nashmi will examine changes in nicotinic receptor expression, assembly, and trafficking in specific brain regions with systemic chronic nicotine infusion.

Program Area: ADDICTION/SUBSTANCE-RELATED DISORDERS\Nicotine

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