Sex Differences in Nicotine Enhancement of Conditioned Place Avoidance Driven by Footshock in Male and Female Rats

Abstract

Introduction: Tobacco use is driven by nicotine, which can enhance the ability of non-nicotine stimuli, including aversive stimuli, to alter behavior. Sex differences exist in the reinforcement enhancement properties of nicotine, but the degree to which this extends to nicotine's ability to enhance behavior driven by aversive stimuli is unclear.

Aims and methods: The current study used adult male and female Sprague-Dawley rats to explore sex differences in nicotine enhancement of footshock (FS)-conditioned place avoidance. FS-conditioned and control rats were tested for conditioned avoidance of FS- or control-paired chambers after injections of saline or nicotine (0.3 mg/kg, subcutaneously).

Results: FS supported place avoidance in both male and female rats, and nicotine enhanced avoidance. Females showed more avoidance after nicotine than males, even in nonconditioned control rats.

Conclusions: These results support the idea that sex differences do exist in nicotine enhancement of aversive stimuli, and suggest the mechanisms through which nicotine supports tobacco dependence in males and females may differ.

Implications: Nicotine enhancement of nondrug stimuli is thought to play a role in tobacco dependence. Yet previous research of enhancement has overwhelmingly used male subjects and appetitive stimuli. Our findings confirm that nicotine also enhances behavior driven by aversive stimuli, and suggests that females may be more susceptible to nicotine enhancement. Such sex differences suggest sex may be an important factor to consider in treating dependence.