1. Mice self-administer amphetamine.
Mice self-administer amphetamine. A, Acquisition of amphetamine self-administration: Following sucrose pretraining, mice were trained to self-administer amphetamine under increasing schedules of reinforcement. After 10 d on FR1, mice that had not achieved stable responding (<20 reinforcers during the last 3 d of FR1) were designated as nonresponding mice and were excluded from the remainder of the behavioral study. Thereafter the saline-treated mice and amphetamine self-administering mice underwent a further 6 d on FR2 and FR5 schedules of reinforcement. Following this acquisition phase, the amphetamine self-administering mice underwent 7 d of abstinence. This was followed by an amphetamine challenge in the same operant boxes and protocol as used during intravenous self-administration to assess the incubation of drug seeking behaviors. The effect of nicotine on this amphetamine challenge was also assessed. B, In comparison with saline-treated mice, amphetamine self-administering mice increased the number of active lever presses. C, The number of inactive lever presses was similar across all groups. D, Compared with saline-treated mice, the amphetamine self-administering mice showed drug-lever association, as assessed by the ratio of active to total (inactive + active) lever presses (%). E, During FR1, FR2, and FR5 schedules of reinforcement, amphetamine self-administering mice achieved a greater number of reinforcers than mice treated with saline, often reaching 50, the maximum allowed during the 2 h session. F, Following forced abstinence, nicotine reduced the total number of active lever presses observed after an amphetamine challenge (G) without altering the inactive lever presses. H, There was no effect of nicotine on lever discrimination, as shown by the ratio of active/total lever presses. I, The administration of nicotine with amphetamine reduced the number of reward-associated cues. The effect of a saline injection on saline-treated mice is shown for comparison with amphetamine self-administering mice. For all panels, $p<0.05, paired t test.
Granville P. Storey et al. eneuro 2016;3:ENEURO
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