Assessment of acute and chronic morphine dependence in male and female mice

The present study compared male and female mice for frequency of naloxone-precipitated jumping and naloxone ED(50) values, two common indices of physical dependence, following acute and chronic morphine administration. Both sexes displayed a positive dose-response relationship between acute morphine and naloxone doses and jumping frequency. There was a significant main effect of sex, with mean jumping frequencies greater in males. The naloxone ED(50) estimate was also fourfold lower in males, indicating greater withdrawal sensitivity than females. Jumping frequencies were similar in male and female saline-treated control mice, discounting initial sex differences as a significant factor in the unequal magnitude and sensitivity in acute morphine dependence between sexes. In contrast, males and females displayed similar mean withdrawal jumping frequencies and naloxone ED(50) values after 3 days of morphine injections. Sex difference in withdrawal jumping was also not observed when morphine treatment was increased to 7 days via daily injection or continuous subcutaneous infusion. The present study demonstrates the development of greater physical dependence in male relative to female mice following acute but not chronic morphine administration.