Time course of dopaminergic hypersensitivity following chronic narcotic treatment.

Guinea pigs were injected SC for 3 weeks with 3 different dosage schedules of morphine or methadone, or with saline. For 8 weeks thereafter they were challenged weekly with the dopamine agonist apomorphine. Hypersensitivity was manifested in more intense stereotypies, as compared to the saline group, by all morphine and methadone groups. Hypersensitivity persisted longer after the termination of methadone treatment (maximum of 8 weeks) than after morphine administration (maximum of 3 weeks). The degree of hypersensitivity, and its duration after treatment, was positively related to methadone dosage. In some groups a period of hyposensitivity was seen following hypersensitivity. These data are interpreted with reference to the hypothesized mechanism underlying the development of hypersensitivity, the different durations of action of morphine and methadone, and the retention of methadone in brain following treatment.