Female rats display dose-dependent differences to the rewarding and aversive effects of nicotine in an age-, hormone-, and sex-dependent manner.

Introduction: The objective of this study was to examine age-, hormone-, and sex-dependent differences to the behavioral effects of nicotine using place-conditioning procedures in female rats.

Methods: Animals received nicotine in their initially non-preferred side and saline on alternate days in their initially preferred side. Following four conditioning trials, rats were re-tested for their preference. To examine developmental differences, we compared the effects of various nicotine doses in female and male adolescent and adult rats. To examine whether our developmental differences are specific to nicotine, we included adolescent and adult females that were conditioned with various amphetamine doses. To examine the influence of hormones on the behavioral effects of nicotine, we compared the effects of various nicotine doses in intact females that were tested during different phases of the estrous cycle and in separate females that were ovariectomized.

Results: The rewarding effects of nicotine were observed at a lower nicotine dose in adolescents versus adults. Amphetamine produced similar rewarding effects across age groups in females. The shifts in preference produced by nicotine were similar across the different phases of estrous. Females lacking ovarian hormones did not display rewarding effects of nicotine at any dose. The rewarding effects of nicotine were enhanced in adult female versus male rats. An intermediate nicotine dose produced rewarding effects in adolescent male but not female rats, suggesting that developmental differences to nicotine may be enhanced in males.

Conclusion: In females, nicotine reward is enhanced during adolescence and is facilitated by the presence of ovarian hormones.