Effect of gonadectomy on discriminative stimulus effects of morphine in female versus male rats

In a previous study, we found sex differences in the potency of morphine as a discriminative stimulus; the present study was designed to determine whe ther sex differences in gonadal hormones contribute to sex differences in m orphine's discriminative effects. Adult female and male rats were gonadecto mized (GNDZ) or sham-gonadectomized (SHAM), and then trained to discriminat e 3.0 mg/kg morphine from saline. The ED50 for morphine discrimination was significantly lower in females than in males (0.66 +/- 0.12 vs. 1.25 +/- 0. 16 mg/kg, respectively); ED50 values in GNDZ rats were slightly higher than in SHAM rats. The time course of morphine discrimination was not significa ntly different in females and males, whether GNDZ or not. The mu agonist fe ntanyl completely substituted for morphine in all rats, with no group diffe rences in ED50 value. The mu agonists buprenorphine and nalbuphine substitu ted for morphine in nearly all females and in all SHAM males, but in only f our of seven GNDZ males. The kappa agonist U69,593 did not substitute for m orphine in rats of any group. Most opioid agonists were significantly more potent in decreasing response rate in males than females, and in GNDZ than SHAM rats; morphine and nalbuphine also increased response rate above contr ol in some females. A pA(2) analysis of naltrexone in combination with morp hine suggested that there were no significant differences among groups in r eceptors at which morphine produced its discriminative stimulus effects. Al though hormone replacement in GNDZ female rats at the end of the study rein stated estrous cycling, it did not substantially alter the ED50 for morphin e discrimination. Thus, sex differences in potency of morphine as a discrim inative stimulus may not be due to sex differences in gonadal hormone milie u. The possibility that sex differences in reinforcement frequency on morph ine versus saline levers caused the sex differences in morphine discriminat ion is discussed. (C) 1999 Elsevier Science Ireland Ltd. All rights reserve d.