Prenatal morphine exposure differentially alters learning and memory in male and female rats

Physiol Behav. 2001 May;73(1-2):93-103. doi: 10.1016/s0031-9384(01)00469-3.


The present study tested the hypothesis that exposure to morphine on prenatal days 11-18 impairs performance on tasks requiring learning and memory in adult male and female rats. In Experiment 1, a symmetrical maze was used to measure learning. In Experiment 2, an eight-arm radial maze was used to assess working spatial memory. The results of Experiment 1 demonstrated that prenatal morphine exposure reduces the time needed to complete the trials, but does not affect the accuracy of performance in male rats. In contrast, prenatal drug treatment had no effects on either the time or the accuracy of performance in female rats. In Experiment 2, both male and female morphine-exposed rats needed more time to complete regular trials (no delay) than controls; however, morphine exposure in male rats did not affect performance on tasks requiring memory, measured with delay trials, but hindered it in ovariohysterectomized (OVX) female rats. In OVX females, replacement injections of both estrogen and progesterone restored the impairment of performance on delay trials produced by prenatal morphine exposure. Thus, the present study demonstrates that prenatal morphine exposure differentially alters performance of adult male and female rats on tasks requiring learning and spatial memory.

Publication types

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

MeSH terms

  • Animals
  • Estrogens / physiology
  • Female
  • Male
  • Maze Learning / drug effects*
  • Mental Recall / drug effects*
  • Morphine / toxicity*
  • Orientation / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Progesterone / physiology
  • Rats
  • Rats, Sprague-Dawley
  • Sex Factors


  • Estrogens
  • Progesterone
  • Morphine