Interaction of methadone, reinforcement history, and variable-interval performance

In the present study, we examined how a reinforcement schedule history that generated high or low rates of responding influenced the effects of acute (Experiment 1) and chronic (Experiment 2) methadone administration. Initially, key-peck responses of pigeons were maintained under a variable-interval 90-s schedule of food presentation, and a methadone dose-response curve was determined with doses of 0.6, 1.2, and 2.4 mg/kg. The pigeons were then exposed, for at least 40 sessions, to either a fixed-ratio 50 schedule or a differential-reinforcement-of-low-rate 10-s schedule, or were given continued exposure to the variable-interval schedule. The methadone dose-response curve was redetermined after all pigeons again were responding under the variable-interval schedule. The effects of two different daily methadone doses (9.0 and 12.0 mg/kg/day) and withdrawal precipitated by naloxone also were assessed. Experience with a fixed-ratio or differential reinforcement of low rate schedule did not result in significantly different response rates under the variable-interval schedule and, in general, the acute effects of methadone did not have differential effects correlated with schedule history. However, for 2 of 4 subjects the rate-decreasing effects of methadone on rates of key pecking were greater following a history of low-rate responding, suggesting a possible interaction between schedule history and effects of methadone. Daily methadone administration under the variable-interval schedule revealed that pigeons with experience under the differential reinforcement of low rate schedule developed more rapid and complete tolerance to the rate-decreasing effects of methadone. Three of the 4 subjects in this group showed rate increases above drug-free baselines during chronic methadone dosing. Pigeons with a history of fixed-ratio responding also developed tolerance to the rate-decreasing effects of methadone but without the subsequent rate increases seen by subjects with low-rate histories. No subjects with variable-interval histories showed complete recovery of drug-free baselines, suggesting that interpolated training under other schedules may attenuate the rate-altering effects of chronically administered drugs. Naloxone (1.0 mg/kg), administered during the chronic methadone phase, resulted in greater disruption of responding by pigeons with a history of low-rate responding, as compared to subjects in the other two groups.(ABSTRACT TRUNCATED AT 400 WORDS)