The Effect of N-acetylcysteine on Behavioral Extinction in Mice

Abstract

The experiments conducted herein examine: (a) the effect of NAC on the extinction and reinstatement of positively reinforced operant behavior maintained by food and (b) the potential for differential effects of NAC across different schedules of reinforcement within an animal model. Forty-seven C57BL/6J mice were trained in an operant paradigm to respond for access to food on an FR-5 or VR-5 reinforcement schedule. Extinction was then implemented concurrent with injections of NAC or vehicle. Following extinction, cued and reward reinstatement sessions were conducted. Data were collected on lever presses on active and inactive levers and head entries into the dipper throughout all phases. Results revealed an ameliorative effect on response frequency during extinction and reinstatement phases for the NAC group for the FR contingency only. No drug effect was evident for the VR schedule, and when FR and VR groups were compared to each other, no significant differential effect of drug by schedule was noted. The significance of results for the FR contingency parallel those found in the drug relapse/reinstatement literature and may suggest consistency across different types of positive reinforcers. However, these results may be tempered by the lack of significant findings for the VR contingency, which more closely parallels naturally occurring schedules of reinforcement. The ambiguity of these findings combined with the potential for NAC to ameliorate undesirable side effects of extinction warrant continued investigation.