Date of Award

2018

Document Type

Open Access Thesis

Department

Psychology

First Advisor

Steven Harrod

Abstract

Administration of nicotine evokes an immense mesolimbic dopamine response that progressively increases, or sensitizes, with repeated drug exposure and can be monitored indirectly through rodent’s motor activity. Sex differences in observed rates of behavioral sensitization in rodents appear to be consistent with epidemiological reports of smoking in humans, which indicate that females are more sensitive to the repeated effects of nicotine. Sex differences in sensitization to nicotine may explain why females progress towards addiction faster than males and so in order to effectively treat and prevent nicotine use in vulnerable populations, it is necessary to identify other factors that can be measured both before and after nicotine exposure to better predict the vulnerability of addiction. The current experiment utilized stepwise regression methods to determine if rodents’ biological sex (male = 41, female = 41), rate of habituation to novelty, and initial hypoactive response to nicotine contribute to predicting the expression of behavioral sensitization after 21 days of once daily intravenous nicotine (0.05 mg/kg) injection. Reductions in the rate of habituation to a novel chamber were predictive of increased horizontal activity sensitization in female rats and may contribute to sex differences in the observed rate of horizontal activity sensitization. Female rats also displayed a reduced sensitivity to the stimulant effects of repeated nicotine on center entries. However, sex differences in center entry and center time sensitization were not related to differences in rate of habituation prior to nicotine exposure. Finally, a reduced hypoactive response to early nicotine exposure predicted greater sensitivity to the stimulant effects of nicotine on horizontal v activity in both sexes. Identifying individuals vulnerable to nicotine addiction prior to or after early drug use may be possible through combining behavioral, physiological, and neural measures and is essential to preventing adverse drug-related health outcomes.

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