Changes in self-stimulation response during chronic morphine treatment and after withdrawal of morphine in rats

Morphine (5-20 mg/kg, s.c.) dose-dependently inhibited the hypothalamic self-stimulation response 1-2 hr after administration of the drug. Thereafter, slight increase in the self-stimulation response was seen 4-8 hr after drug administration. The depressant effect induced by 10 mg/kg, s.c. of morphine on the self-stimulation response was antagonized by 1 mg/kg, s.c. of levallorphan. Repeated administration of morphine (10 mg/kg, s.c.) resulted in an increase of the self-stimulation response. The self-stimulation response rate was increased significantly 24 and 48 hr after withdrawal of morphine in chronic-morphine-treated rats; In these rats, the initial dose of morphine (10 mg/kg, injected s.c. twice daily 7 days a week) was increased gradually until at the end of 5 weeks, each dose was 50 mg/kg, s.c.