Gender differences in the reinforcing properties of morphine

The purpose of the present studies was to examine whether gender difference s could be observed in an important aspect of morphine's pharmacology: its reinforcing properties. Our results showed that morphine served as a positi ve reinforcing agent in both male and female rats in a place conditioning p aradigm, but that the dose-response curves displayed marked sex-related dif ferences. At doses from 0.2 up to 10.0 mg/kg, morphine induced an equally s trong preference for the drug-associated chamber in males and females. Howe ver, as the dose was increased from 10-17.5 mg/kg, morphine ceased to act a s a positive reinforcer in males. In contrast, a Very strong preference for the morphine-associated chamber was still observed in females at doses up to 30 mg/kg. No gender differences in the blood and brain levels of morphin e were observed subsequent to morphine administration during the conditioni ng phase, suggesting that pharmacokinetic factors were not involved in the sex-related differences observed. Consequently, these results suggest that there are intrinsic sex-linked differences in the doses of morphine that ca n induce a preference for the drug-associated chamber in a place-conditioni ng paradigm that are most likely related to differences in the sensitivity of the central nervous system to morphine's reinforcing properties in males and females. (C) 1999 Elsevier Science Inc.