Amplified reacquisition of nicotine self-administration in rats by repeated stress during abstinence

Quitting smoking is often very challenging, leading to frequent relapse. Exposure to acute and chronic stress during abstinence increases the likelihood of relapse to smoking. In rodents, stress acutely reinstates nicotine seeking after extinction of nicotine self-administration (SA). However, whether reacquisition of nicotine taking is amplified by chronic stress during abstinence from nicotine SA has not been determined in animals. We sought to determine effects of repeated restraint stress during abstinence on reacquisition of nicotine SA. Rats acquired nicotine SA (23 h/day) under a fixed-ratio (FR) 5 schedule of reinforcement, which was followed by an abstinence phase. Restraint (0, 2, and 4 times) was administered during abstinence. Animals reacquired nicotine SA, first under a progressive ratio (PR) schedule, beginning immediately after the final stress, followed by an FR5 schedule. In another experiment, reacquisition (FR5) began 24 h after the final stress. No PR testing was conducted. Four restraint stress exposures during abstinence, but not only two, enhanced reacquisition of nicotine SA by increasing nicotine injections under a PR schedule beginning immediately after the final stress (p < 0.05) followed by increasing nicotine intake under an FR5 schedule (p < 0.05). This was observed even when the final stress and reacquisition trial were separated by 24 h. Moreover, repeated stress-induced nicotine taking during the behaviorally inactive phase (i.e., lights on) of the 24-h diurnal cycle. Chronic (i.e., repeated) stress during abstinence promotes reacquisition of nicotine SA and affects diurnal pattern of nicotine intake.