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Drug Alcohol Depend. 2004 Jun 11;74(3):297-309.

Effects of chronic methadone treatment on cocaine- and food-maintained responding under second-order, progressive-ratio and concurrent-choice schedules in rhesus monkeys.

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  • 1Alcohol and Drug Abuse Research Center, McLean Hospital, Harvard Medical School, Belmont, MA 02478-9106, USA. negus@mclean.harvard.edu


The effects of chronic infusion with saline or methadone (0.032-1.0 mg/kg/h) were examined on cocaine- and food-maintained responding in rhesus monkeys using three procedures. In one procedure, cocaine injections (0.0032-0.032 mg/kg per injection) and food pellets were available under a second-order schedule during alternating daily sessions. During saline treatment, cocaine maintained a dose-dependent increase in the number of cocaine injections per day, and monkeys usually responded for the maximum number of pellets. Methadone dose-dependently decreased cocaine self-administration, and methadone doses that decreased cocaine self-administration had variable effects on food-maintained responding. In the second procedure, 0.032 mg/kg per injection cocaine or food pellets were available under a progressive-ratio schedule. During saline treatment, cocaine and food maintained similar break points. Methadone produced a dose-dependent and non-selective decrease in break points maintained by both cocaine and food. In the third procedure, cocaine injections (0-0.1 mg/kg per injection) and food pellets were available under a concurrent-choice schedule. During saline treatment, increasing unit doses of cocaine produced a dose-dependent increase in cocaine choice. Methadone had little effect on the cocaine choice dose-effect curve up to doses that eliminated responding. These results provide little evidence to suggest that chronic methadone altered the reinforcing effects of cocaine; rather methadone appeared to non-selectively decrease rates of operant responding.

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