Abstract
Concurrent abuse of cocaine and opioids is frequently observed clinically, and we have developed a model of “speedball” self-administration involving the simultaneous injection of cocaine and heroin combinations in rhesus monkeys (Mello et al.(1995)JPharmacol Exp Ther274:1325). 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 cocaine [0.001, 0.01 or 0.10 mg/kg/inj] and heroin [0.0001–0.032 mg/kg/inj]. 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/kg/inj). Drug and food (1-g banana pellets) self-administration were maintained on a second-order FR4 (VR16:S) schedule in four 1-hr sessions each day. Each buprenorphine or saline control treatment was evaluated for 10 consecutive days, and monkeys returned to base-line performance between each treatment condition. Buprenorphine (0.075–0.75 mg/kg/day) selectively reduced self-administration of speedball combinations of low-dose cocaine (0.001 mg/kg/inj) and heroin (0.001 or 0.0032 mg/kg/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 approximately 1 log unit to the right. Buprenorphine treatment was less effective in decreasing responding maintained by speedball combinations of heroin 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 downward (P < .01–.001) and to the right. Both speedball and heroin self-administration were associated with dose-dependent decreases in food-maintained responding during saline control treatment. However, food-maintained responding was often higher than control levels during buprenorphine treatment (P < .05–.001), which suggests that buprenorphine antagonized the rate-decreasing effects of speedballs and of heroin. Buprenorphine’s selective reduction of speedball and heroin self-administration is consistent with clinical treatment trials in opioid abusers and polydrug abusers. Thus, these primate models of speedball and heroin self-administration should be useful for preclinical evaluation of novel drug abuse treatment medications.
Footnotes
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Send reprint requests to: Nancy K. Mello, Ph.D., Alcohol and Drug Abuse Research Center, Harvard Medical School-McLean Hospital, 115 Mill Street, Belmont, MA 02178.
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↵1 This research was supported in part by grants K05-DA 00101, P50-DA 04059 and RO1-DA 02519 from the National Institute on Drug Abuse, National Institutes of Health. Preliminary data were presented to the College on Problems of Drug Dependence in 1995 and 1997 and to the American College of Neuropsychopharmacology in 1996.
- Abbreviations:
- ANOVA
- analysis of variance
- FR
- fixed ratio
- VR
- variable ratio
- DSM-III-R
- Diagnostic and Statistical Manual of Mental Disorders (3rd ed-revised)
- inj
- injection
- Received September 2, 1997.
- Accepted January 7, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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