Time-Dependent Inhibition by Naloxone, an Opiate Receptor Antagonist, of the Sensitization to Morphine-Induced Ambulatory Stimulation

Abstract

Abstract:A significant sensitization to the ambulation-stimulating effect of morphine (10 mg/kg s.c.), a narcotic analgesic drug with agonistic action on opiate receptors, was produced when mice were repeatedly administered morphine at intervals of 3 days, and their ambulation was measured for 3 hr in an activity cage of 20 cm in diameter after each administration. Naloxone (0.01-1 mg/kg s.c.), an opiate receptor antagonist, blocked the morphine-induced ambulation in a dose-dependent manner. The mice treated with naloxone at post-morphine period of 3/4 hr and later showed a strong ambulatory sensitization as high as that in the mice repeatedly given morphine alone. The treatment with naloxone at post-morphine period of 1/2 hr caused a partial sensitization, and at 0-1/3 hr no significant sensitization. The repeated administrations of naloxone alone or saline caused no significant change in the sensitivity to morphine. These results suggest that experience of morphine effect and the resultant ambulation for 1/2 hr prior to the peak effect is important for induction of the sensitization to the ambulation-increasing effect of morphine in mice. This finding also indicates that the reward effect of morphine appears in the early post-morphine period prior to the peak effect, which is the essential factor for induction and maintenance of the abuse and dependence of narcotic analgesic drugs such as morphine and heroin.