Experiment 6: Cue-Induced Methamphetamine Seeking in Rats

Additional groups of rats were used to assess the effects of BCP pretreatment on contextual cue-induced METH-seeking behavior. This “incubation of craving” model was chosen because it mimics relapse in humans after forced abstinence (Altshuler et al., 2021). In addition, we have found over many years of experience that contextual cue-induced drug seeking is more robust than classical cue-induced reinstatement responding, and therefore, it is a more sensitive measure of cue-induced changes in drug-seeking behavior. After stable METH self-administration was achieved under a FR2 schedule of reinforcement, rats underwent forced abstinence in their home cages. After 21 days of withdrawal from METH self-administration, rats were divided into four experimental groups; each group received either vehicle (5% Kolliphor solution) or one of the three doses of BCP (25, 50, 100 mg/kg). 30 min after the injection on the test day, the rats were re-placed into the same self-administration chambers. Contextual cue-induced drug seeking was conducted under conditions identical to that of self-administration, except that responses on the active lever (under a FR2 schedule) resulted in contingent presentation of the cues without METH availability (no infusions). Responses on the inactive lever were recorded but had no programmed consequences. Each reinstatement test lasted for 3 h.