Gender differences and the role of estrogen in cognitive enhancements with nicotine in rats

Research has reported that nicotine can increase accuracy, response times and rates of learning with evidence of different effects on males and females. The goal of our research was to study further sex differences by examining the role played by estrogen in the effects of nicotine on learning and memory in female rats. In experiment 1, 48 male and female rats were administered 0.3 mg or 0.7 mg/kg bwt of nicotine (nic) or vehicle only (veh) and tested in a visual spatial orientation (VSO) paradigm designed to maximize the benefits of nicotine on spatial working memory. Females exposed to 0.3 mg nic performed superior to all other groups of both genders. In experiment 2, ovariectomized females (N = 40) were exposed to 30 µg estradiol/kg bwt (E2), 3 mg nicotine/kg bwt, a combination of both E2 and nic, or veh, and tested as in experiment 1. The rankings of scores in the VSO task by group were E2 + nic > nic alone > E2 alone > veh. The E2 + nic combination group also demonstrated the highest rate of acquisition. Collectively, the findings suggest that estrogen can synergize the ability of chronic nicotine to enhance acetylcholine–hippocampal interactions underlying performance in the VSO paradigm.