Sex differences in development of morphine tolerance and dependence in therat

Rationale: Several investigators have shown that male rodents are more sens itive than females to morphine's antinociceptive effects. Objective: The pr esent study was conducted to determine whether this sex difference is stabl e after chronic morphine treatment. Results: Acutely administered morphine produced significantly greater hotplate and tail withdrawal antinociception in males than in females. In contrast, there were no sex differences in mo rphine's hotplate or tail withdrawal effects under repeated (l-week interva l) dosing conditions. In a separate group of rats, after 2 weeks of twice-d aily morphine treatment (10-20 mg/kg per injection), the ED,, for morphine' s antinociceptive effects increased approximately 6.9-fold in males versus only 3.7-fold in females; chronic morphine treatment also disrupted the est rous cycle of females. In a separate group of rats treated with 10 mg/kg mo rphine twice daily for 5 days, treatment with naloxone (1.0 mg/kg) on day 6 produced greater withdrawal scores in males than in females. Conclusions: These experiments demonstrate sex differences in development of tolerance t o and dependence on morphine in the rat.