Abstract
RATIONALE: Dependence can develop during chronic opioid use, and the emergence of withdrawal might promote drug taking. OBJECTIVE: This study examined how chronic morphine administration or withdrawal modified self administration of heroin or cocaine. METHODS: Four monkeys responded under a fixed ratio 10 schedule to receive i.v. infusions of heroin (0.56-560 microg/kg/infusion) or cocaine (1-100 microg/kg/infusion). Monkeys received morphine twice daily; the final dose was 10 mg/kg/12 h. Dose-effect curves for heroin or cocaine were determined in 150-min sessions throughout morphine administration and during temporary suspension when withdrawal signs were also monitored. Heroin dose-effect curves and withdrawal signs were determined daily following termination of morphine administration. RESULTS: Before monkeys received morphine, heroin, and cocaine maintained responding with unit doses of 1.78 microg/kg of heroin and 10 microg/kg/injection of cocaine resulting in, on average, 13.4 and 20.8 infusions, respectively. When monkeys received morphine daily, self administration of heroin and cocaine decreased to, on average, 3.1 and 11.3 infusions, respectively. Responding for heroin or cocaine recovered following temporary (17-53 h) suspension of morphine administration. The number of heroin infusions and total withdrawal signs increased when morphine administration was terminated. Withdrawal signs peaked 3-4 days after morphine; however, the number of infusions remained elevated for 8 weeks. CONCLUSIONS: Changes in self administration responding did not precisely covary with signs of withdrawal and responding for small doses of heroin persisted long after discontinuation of morphine, suggesting that non-pharmacologic (e.g., conditioned reinforcing) effects might contribute to the maintenance of lever pressing under these conditions.