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Speaker

Daniel McGehee

University of Chicago
Neurobiology
773-834-0790
dmcgehee@uchicago.edu
Cellular mechanisms of nicotine addiction
The potent behavioral effects of nicotine are clearly evidenced by the widespread use of tobacco products. Tobacco use is the leading cause of preventable death in the industrialized world, which highlights the importance of understanding how nicotine works. Many brain neurons express receptors that bind nicotine with high affinity, and these receptors are ultimately responsible for the behavioral effects of nicotine. The normal activator of these receptors is the neurotransmitter acetylcholine, and there are several nicotinic acetylcholine receptors (nAChR) subtypes expressed in the CNS. Determining the nAChR subtypes that underlie the various physiological effects of nicotine may help identify new methods to help people quit smoking. Nicotine reinforces smoking behavior primarily by activating nAChRs in the dopamine reward pathways. Dopamine release has been shown to be important for the rewarding feelings associated with many drugs of abuse, including nicotine. We have found that in addition to directly exciting the dopamine neurons, nicotine also alters the excitatory and inhibitory drive to those cells. In fact, nicotine causes a persistent increase in excitatory drive while simultaneously diminishing the inhibitory component. Thus, nicotine enhances dopamine release from reward areas of the brain by several different but overlapping mechanisms that ensure potent and persistent behavioral effects.
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