Reward-enhancing effects of d-amphetamine and its interactions with nicotine were greater in female rats and persisted across schedules of reinforcement

Nicotine enhances the value of environmental stimuli and rewards, and reward enhancement can maintain nicotine consumption. Stimulants such as d-amphetamine are misused more by women and are commonly co-used with nicotine. d-Amphetamine potentiates nicotine's effects in human and animal research. To date, there are no published studies examining this interaction in a reward-enhancement task. The current study sought to investigate the reward-enhancing effects of nicotine alongside and coadministered with d-amphetamine. Further, we evaluated the persistence of reward enhancement across ratio and temporal schedules of reinforcement. We used 10 male and 10 female Sprague-Dawley rats. Enhancement was assessed within subjects by examining active lever pressing for a visual stimulus reinforcer on variable ratio 3, variable interval 30 s and variable time 30 s - variable ratio 3 schedules. Before 1-h sessions, rats received one injection of saline, 0.1 or 0.3 mg/kg d-amphetamine and one of saline or 0.4 mg/kg nicotine, making six possible drug combinations (saline + saline, saline + nicotine, 0.1 d-amphetamine + aline, 0.1 d-amphetamine + nicotine, 0.3 d-amphetamine + saline and 0.3 d-amphetamine + nicotine) experienced in a randomized order by each rat. When d-amphetamine was coadministered with nicotine, we found an interaction effect on reward enhancement that persisted across schedules of reinforcement. Males and females exhibited reward enhancement by 0.3 d-amphetamine, while only females showed reward enhancement by 0.1 d-amphetamine. Further, females responded more for the visual stimulus than males in all d-amphetamine conditions. Future studies should assess how reward enhancement is involved in high nicotine-amphetamine comorbidity rates and enhanced amphetamine misuse in women.