Effects of indatraline and buprenorphine on self-administration of speedball combinations of cocaine and heroin by rhesus monkeys.
The simultaneous intravenous (i.v.) administration of heroin and cocaine, called a "speedball," is often reported clinically, and identification of effective pharmacotherapies is a continuing challenge. We hypothesized that treatment with combinations of a dopamine reuptake inhibitor, indatraline, and a mu partial agonist, buprenorphine, might reduce speedball self-administration by rhesus monkeys more effectively than either drug alone. Speedballs (0.01 mg/kg/inj cocaine + 0.0032 mg/kg/inj heroin) and food (1 g banana pellets) were available in four daily sessions on a second-order schedule of reinforcement [fixed ratio (FR)4; variable ratio (VR)16:S]. Monkeys were treated for 10 days with saline or ascending dose combinations of indatraline (0.001-0.032 mg/kg/day) and buprenorphine (0.00032-0.01 mg/kg/day). Two combinations of indatraline (0.32 and 0.56 mg/kg/day) + buprenorphine (0.10 and 0.18 mg/kg/day) significantly reduced speedball self-administration in comparison to the saline treatment baseline (p <.01-.001), whereas the same doses of each compound alone had no significant effect on speedball-maintained responding. Daily treatment with 0.56 mg/kg/day indatraline + 0.18 mg/kg/day buprenorphine produced a significant downward shift in the speedball dose-effect curve (p <.01) and transient changes in food-maintained responding. These findings suggest that medication mixtures designed to target both the stimulant and opioid component of the speedball combination may be an effective approach to polydrug abuse treatment.
Mello
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Alcohol and Drug Abuse Research Center, McLean Hospital-Harvard Medical School, Belmont, MA 02478, USA.
Negus
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SS
D000818:Animals; D002047:Buprenorphine / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004347:Drug Interactions / Q000502:physiology*; D005260:Female; D003932:Heroin / Q000494:pharmacology; D006556:Heroin Dependence / Q000188:drug therapy* / Q000503:physiopathology; D007189:Indans / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008744:Methylamines / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology*; D012646:Self Administration
D018765:Dopamine Uptake Inhibitors; D004338:Drug Combinations; D007189:Indans; D008744:Methylamines; D009294:Narcotics; D014179:Neurotransmitter Uptake Inhibitors; D002047:Buprenorphine; C418119:indatraline; D003932:Heroin; D003042:Cocaine