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Impulsivity as a risk factor for nicotine dependence

Institution: University of California, San Diego
Investigator(s): Svetlana Semenova, Ph.D.
Award Cycle: 2009 (Cycle 18) Grant #: 18KT-0022 Award: $270,000
Subject Area: Nicotine Dependence
Award Type: New Investigator Awards

Initial Award Abstract
Scientific studies have shown that if a person has a personality that makes him or her more likely to engage in impulsive behaviors, then that individual is more likely to begin tobacco smoking and become dependent on nicotine contained in tobacco smoke. Little is known about the mechanisms in the brain that link impulsivity with nicotine dependence. How differences in impulsivity influence the rewarding effects of nicotine and the negative effects experienced when trying to quit smoking are also poorly understood. Basic science research offers the opportunity to examine the mechanisms of nicotine dependence, and to investigate impulsivity as a risk factor that may lead to addiction. Our project aims to investigate the link between impulsivity and nicotine dependence by studying the effects of nicotine and nicotine withdrawal in subjects that differ in their degree of impulsivity.

We will select high (HI) and low (LI) impulsive subjects in behavioral tests assessing two distinct types of impulsivity, namely poor inhibitory control and impulsive choice that have been implicated in tobacco smoking. Then, we will assess emotional responses to nicotine and nicotine withdrawal in HI and LI subjects. The intracranial self-stimulation procedure provides a valid, reliable and quantitative measure of the emotional response to nicotine and nicotine withdrawal that is called reward thresholds. Threshold lowering reflects an enhancement in the reward value of the stimulation during nicotine exposure. Threshold elevations, a measure of reward deficits, reflect a decrease in the reward value of the stimulation during nicotine withdrawal. These measures have translational value because they assess brain reward function that may be differentially dysregulated in high and low impulsive smokers. Further, both nicotine dependence and impulsive behavior has been linked to decreases in the levels of norepinephrine (NE), one of several chemicals in the brain that send information from one nerve cell to another. We will explore how increases in NE levels induced by administration of atomoxetine, a NE reuptake blocker, and idazoxan, a blocker at α2A NE receptors, will affect the nicotine-induced reward enhancement and nicotine withdrawal-induced reward deficits in HI and LI subjects.

The proposed project will provide insights on brain reward function in subjects with different levels of impulsivity in response to nicotine and nicotine withdrawal, and on the role of two distinct impulsivity types in the development of nicotine dependence. We will also determine whether pharmacological treatments that increase NE neurotransmission will be differentially effective against nicotine withdrawal in subjects differing in impulsivity levels as they reduce both impulsivity and nicotine withdrawal symptoms. Thus, the results of the proposed work may lead to new strategies and therapies for the treatment of nicotine dependence in high and low impulsive smokers.