Nicotine effects on gene expression and metaplasticity
Initial Award Abstract
One of the most sinister aspects of tobacco is that it is so highly addictive. Addiction to nicotine is central to all tobacco-related disease; therefore, understanding the mechanisms of nicotine addiction will help us generate therapies aimed at alleviating the desire to use tobacco. It is clear that addiction to tobacco is very strong and very long-lasting: ex-smokers can relapse years after smoking cessation. This long-lasting effect of nicotine or other addictive drugs can be seen as a memory for the drug taking behavior. We know quite a bit about the mechanisms neurons in the brain use to produce memories and, intriguingly, much recent research has indicated that addictive drugs recruit very similar mechanisms to produce their long-lasting effects. Our lab has a strong track-record in examining the cellular and molecular mechanisms in neurons that produce long-term alterations in their function that are related to learning and memory. In this proposal I suggest experiments aimed using this expertise to look at the cellular and molecular responses of neurons to chronic nicotine exposure. In particular, addictive drugs seem to regulate which genes in neurons are expressed: I will examine the mechanisms by which nicotine regulates gene expression. Understanding how neurons respond to chronic nicotine exposure, as occurs in the brains of smokers, will provide important insight into the mechanisms of addiction. One goal of understanding the changes within cells that mediate addiction to nicotine is to generate therapies that target these changes to prevent or break the addiction. |
|L-type calcium channel ligands block nicotine-induced signaling to CREB by inhibiting nicotinic receptors
|Authors: Wheeler, D.G., Barrett, C.F. and Tsien, R.W.