THE EFFECTS OF BUPRENORPHINE ON SELF-ADMINISTRATION OF COCAINE AND HEROIN SPEEDBALL COMBINATIONS AND HEROIN ALONE BY RHESUS-MONKEYS

Concurrent abuse of cocaine and opioids is frequently observed clinica lly, and we have developed a model of ''speedball'' self-administratio n involving the simultaneous injection of cocaine and heroin combinati ons in rhesus monkeys (Mello et al. (1995) J Pharmacol Exp Ther 274:13 25). In the present study, we evaluated the effects of buprenorphine ( 0.0075-0.75 mg/kg/day i.v.) and saline on speedball combinations of co caine [0.001, 0.01 or 0.10 mg/kg/inj] and heroin [0.0001-0.032 mg/kg/i nj]. We also examined the effects of buprenorphine (0.075 and 0.237 mg /kg/day i.v.) on self-administration of heroin alone (0.0001-0.01 mg/k g/inj). Drug and food (1-g banana pellets) self-administration were ma intained on a second-order FR4 (VR16:S) schedule in four 1-hr sessions each day. Each buprenorphine or saline control treatment was evaluate d for 10 consecutive days, and monkeys returned to base-line performan ce between each treatment condition. Buprenorphine (0.075-0.75 mg/kg/d ay) selectively reduced self-administration of speedball combinations of low-dose cocaine (0.001 mg/kg/inj) and heroin (0.001 or 0.0032 mg/k g/inj) (P <.05-.01), and buprenorphine (0.237 mg/kg/day) shifted dose- effect curves for speedball combinations of cocaine (0.001 mg/kg/inj) and heroin (0.0001-0.032 mg/kg/inj) downward (P <.05-.01) and approxim ately 1 log unit to the right. Buprenorphine treatment was less effect ive in decreasing responding maintained by speedball combinations of h eroin and 0.01 and 0.10 mg/kg/inj cocaine. Buprenorphine treatment (0. 075 and 0.237 mg/kg/day) also shifted the heroin dose-effect curve dow nward (P <.01.-001) and to the right. Both speedball and heroin self-a dministration were associated with dose-dependent decreases in food-ma intained responding during saline control treatment. However, food-mai ntained responding was often higher than control levels during bupreno rphine treatment (P <.05-.001), which suggests that buprenorphine anta gonized the rate-decreasing effects of speedballs and of heroin. Bupre norphine's selective reduction of speedball and heroin self-administra tion is consistent with clinical treatment trials in opioid abusers an d polydrug abusers. Thus. these primate models of speedball and heroin self-administration should be useful for preclinical evaluation of no vel drug abuse treatment medications.