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Individual and gender differences in nicotine sensitivity

Institution: University of California, Irvine
Investigator(s): Minjung Park, Ph.D.
Award Cycle: 2003 (Cycle 12) Grant #: 12FT-0247 Award: $69,495
Subject Area: Nicotine Dependence
Award Type: Postdoctoral Fellowship Awards

Initial Award Abstract
Gender and stress responsivity are important regulatory factors in human smoking behavior. Both animal and human studies clearly indicate that females respond differently to nicotine, the psychoactive component of tobacco. For example, women are more sensitive to mood changes after smoking and during smoking abstinence than men. Animal research also indicates that the motivation to get nicotine is greater in females. There exist dynamic, bi-directional interactions between nicotine and the stress system. Nicotine activates the stress system and increases glucocorticoid release. Glucocorticoid, in turn, modulates nicotine sensitivity. Biological responses to stress are greatly different between individuals, and are implicated in differential sensitivity toward abused drugs. The development of the stress system is strongly influenced by early rearing conditions. Using animal models of early environmental manipulation, studies have shown that these environmental factors contribute to long-term changes in the developing offspring’s ability to deal with stress and vulnerability to abused drugs in adulthood. Recently, I have found that early environmental manipulation differentially affects male and female rats. Early postnatal handling dampened endocrine stress reactivity in male offspring while potentiating stress reactivity in female littermates. These differences in stress reactivity are also reflected in brain activity. Although nicotine is known to modulate the stress system, there has been no systemic analysis of nicotine effects in these animals. We will test the hypothesis, using this animal model, that male and female rats with differential stress reactivity respond to nicotine with different sensitivity. We will measure hormonal, neuroanatomical and behavioral changes after nicotine administration and, ultimately, compare the differences between male and female’s response to the reinforcing effect of nicotine. Data from the current study will provide evidence as to differential stress reactivity may be a regulating factor in initiation of tobacco use and progression to nicotine addiction. Furthermore, data from this study will improve understanding of how nicotine addiction may differ by gender. The combined biochemical and behavioral data from this study should provide a conceptual framework to develop more effective tobacco use prevention and interventions in gender-specific and individual-specific ways.