Cocaine-induced reinstatement during limited and extended drug access conditions in rhesus monkeys

Abstract

The progression of addiction from controlled to compulsive drug use leads to serious adverse consequences, including a greater propensity to relapse to drug use after sustained periods of abstinence. The present study assessed the potential effects of cocaine self-administration history on the magnitude and persistence of cocaine-induced reinstatement in rhesus monkeys (n = 6). During a 3-month period of limited access to cocaine self-administration under a second-order schedule, subjects could take a maximum of 0.5 mg/kg per session 5 days per week. During a subsequent 3-month period of extended access to cocaine self-administration, subjects could take an additional 3.0 mg/kg under a fixed-ratio 20 schedule 3 days per week. Reinstatement effects were evaluated on six separate occasions that included limited and extended access conditions. Saline was substituted for cocaine, and once extinction criteria were met (response rates <20% of cocaine-maintained rates), response-independent cocaine (0.1 mg/kg) was administered i.v. prior to extinction sessions. Reinstatement was defined as a restoration of drug-appropriate responding above extinction criteria. Reinstatement experiments were conducted repeatedly on a daily basis until response rates returned to extinction levels. Peak response rates provided a measure of reinstatement magnitude whereas number of sessions required to meet extinction levels provided a measure of reinstatement persistence. Both the magnitude and persistence of reinstatement were consistent across all determinations regardless of drug history. The results indicate that reinstatement under the second-order schedule is remarkably stable even when supplemental drug intake is provided over several months.