Gender differences in the reinforcing properties of morphine

Pharmacol Biochem Behav. 2000 Jan 1;65(1):91-6. doi: 10.1016/s0091-3057(99)00174-4.


The purpose of the present studies was to examine whether gender differences could be observed in an important aspect of morphine's pharmacology: its reinforcing properties. Our results showed that morphine served as a positive reinforcing agent in both male and female rats in a place conditioning paradigm, but that the dose-response curves displayed marked sex-related differences. At doses from 0.2 up to 10.0 mg/kg, morphine induced an equally strong preference for the drug-associated chamber in males and females. However, as the dose was increased from 10-17.5 mg/kg, morphine ceased to act as 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 morphine were observed subsequent to morphine administration during the conditioning 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 can induce a preference for the drug-associated chamber in a place-conditioning 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Brain / metabolism
  • Conditioning, Psychological / drug effects*
  • Dose-Response Relationship, Drug
  • Female
  • Male
  • Morphine / pharmacokinetics
  • Morphine / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Reinforcement, Psychology*
  • Sex Characteristics


  • Morphine