Sex differences in the vulnerability to drug abuse: a review of preclinical studies

Neurosci Biobehav Rev. 2004 Oct;28(6):533-46. doi: 10.1016/j.neubiorev.2004.08.001.


Clinical and preclinical findings indicate that males and females differ on several aspects of drug reinforcement. Females are more vulnerable than males during transition periods of drug use that are characteristic of drug addiction and relapse. Females are also more sensitive than males to the reinforcing effects of stimulants. It has been suggested that ovarian hormones contribute to the mechanisms of action underlying these sex differences. This review examines the preclinical literature on sex differences and ovarian hormonal influences on drug self-administration in animals. It summarizes the findings on the effects of these variables during different phases of drug addiction. Possible differences in the mechanisms of action of drugs of abuse due to interactions with sex differences or ovarian hormonal factors are considered. The animal literature on sex differences in drug abuse treatment effectiveness is also discussed.

Publication types

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

MeSH terms

  • Animals
  • Estrogens / pharmacology
  • Female
  • Humans
  • Male
  • Reinforcement, Psychology
  • Self Administration
  • Sex Characteristics
  • Substance-Related Disorders / physiopathology*
  • Substance-Related Disorders / psychology*
  • Substance-Related Disorders / therapy


  • Estrogens