SEX-DIFFERENCES IN DISCRIMINATIVE STIMULUS EFFECTS OF MORPHINE IN THERAT

Nine female and ten male rats were trained to discriminate 3.0 mg/kg s ,c. morphine from saline, The six female rats that acquired and mainta ined the morphine discrimination did so in significantly fewer session s than the eight males did (28+/-5 vs 51+/-9 sessions, respectively), and the ED50 for morphine substitution was significantly lower in fema les (0.69+/-0.15 vs 1.28+/-0.20 mg/kg), The time course of morphine su bstitution was approximately equivalent in females and males, The mu a gonist fentanyl completely substituted for morphine in both sexes, wit h no sex difference in potency to substitute for morphine, The mu agon ist buprenorphine partially or completely substituted for morphine in all females and five of six males, but at a lower dose in females (ED5 0 0.009+/-0.002 vs 0.019+/-0.006 mg/kg). The delta agonist BW373U86 pa rtially substituted for morphine in both sexes, with no potency differ ences; the k agonist U69,593 and the non-opioid cocaine did not substi tute for morphine in either sex, On a test of spontaneous locomotor ac tivity, morphine increased locomotion to a slightly but not significan tly greater extent in males than in females, Morphine also produced si gnificantly greater hotplate antinociception in males than in females, Further drug discrimination training with a lower dose of morphine, 1 .0 mg/kg, decreased the ED50 for morphine substitution in females and males to 0.26+/-0.06 vs 0.45+/-0.11 mg/kg, respectively (not significa nt), In a separate group of age-matched rats, there was no sex differe nce in brain or plasma levels of morphine measured via HPLC 20 min pos t-injection, the pretreatment time used to examine behavioral effects of morphine, The HPLC results, plus the fact that sex differences were not the same for all behavioral effects of morphine, suggest that sex differences in discriminative stimulus effects of morphine are not du e to differential pharmacokinetics. The possibility that sex differenc es in morphine discrimination reflect sex differences in opioid recept or pharmacology, or differential reinforcement between morphine and sa line levers for males but not females, is discussed.