Assessment of the impact of pattern of cocaine dosing schedule during conditioning and reconditioning on magnitude of cocaine CPP, extinction, and reinstatement

Abstract

We sought to examine the impact of differing cocaine administration schedules and dosing on the magnitude of cocaine conditioned place preference (CPP), extinction, and stress- and cocaine-induced reinstatement of CPP. First, in C57Bl/6J mice, we investigated whether total cocaine administration or pattern of drug exposure could influence the magnitude of cocaine CPP by conditioning mice with a fixed-low dose (FL; 7.5mg/kg; total of 30mg/kg), a fixed-high dose (FH; 16mg/kg; total of 64mg/kg), or an ascending dosing schedule (Asc; 2, 4, 8, and 16mg/kg; total of 30mg/kg). Next, we investigated if cocaine or saline is more effective at extinguishing preference by reconditioning mice with either a descending dosing schedule (Desc; 8, 4, 2, and 1mg/kg) or saline. Finally, we examined if prior conditioning and reconditioning history alters stress (~2-3-min forced swim test) or cocaine-induced (3.5mg/kg) reinstatement. We replicated and extended findings by Itzhak and Anderson (Addict. Biol. 17(4): 706-16, 2011) demonstrating that Asc conditioning produces a greater CPP than either the FL or FH conditioning schedules. The magnitude of extinction expressed was similar in the Desc reconditioned and saline groups. Moreover, only the saline, and not the Desc reconditioned mice, showed stress and cocaine-induced reinstatement of CPP. Our results suggest that the schedule of cocaine administration during conditioning and reconditioning can have a significant influence on the magnitude of CPP and extinction of preference and the ability of cocaine or a stressor to reinstate CPP.