Development of behavioral tolerance to morphine and methadone using the schedule-controlled behavior of the pigeon.

Abstract

A multiple fixed-ratio, fixed-interval schedule of food presentation was used to study the development of behavioral tolerance to daily injections of equipotent doses of morphine and methadone in the pigeon. There was evidence that tolerance was developing to the rate-decreasing effects of both drugs after a single injection. Tolerance to morphine developed more rapidly during the first week of injections than did tolerance to methadone. Tolerance to the depressant effects of morphine and methadone was less complete under the fixed-ratio component of the schedule than under the fixed-interval component. After repeated injections, increases in the rate of responding were observed in some birds. These increases depended on the bird, rather than on the narcotic. Thus, the development of tolerance was a function of the drug, of the individual bird, and of the schedule maintaining the behavior.