Reinstatement of cocaine self-administration in rats: sex differences

Psychopharmacology (Berl). 2000 Feb;148(2):196-200. doi: 10.1007/s002130050042.


Rationale: Results obtained with both humans and animals suggest that rates of relapse, or levels of reinstatement responding, may differ between males and females. However, the results obtained with humans are equivocal, and few studies have compared male and female animals on reinstatement responding.

Objectives: The present experiment was designed to compare male (n=8) and female (n=8) rats on reinstatement of extinguished cocaine-reinforced responding.

Methods: Reinstatement of responding was examined using a priming model in which lever pressing for cocaine (0.2 mg/kg) was extinguished by replacing cocaine infusions (2 h) with saline infusions (5 h). After responding extinguished during hour 3, reinstatement of responding was tested by administering one of several priming injections of cocaine (0.32, 1.0 and 3.2 mg/kg) or an equal volume of saline.

Results: Although males and females did not differ in the number of saline infusions self-administered after either saline or 0.32 mg/kg cocaine-priming injections, female rats self-administered significantly more saline infusions than males after 1.0 mg/kg and 3.2 mg/kg cocaine-priming injections. Additionally, the effects of 0.32 mg/kg cocaine-priming injections were significantly different from those of saline-priming injections for female, but not male, rats. There was no significant difference between males and females in total cocaine self-administered during hours 1 and 2.

Conclusions: These findings indicate that female rats are more sensitive than males during the reinstatement phase of drug abuse.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Cocaine / administration & dosage*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extinction, Psychological / drug effects*
  • Female
  • Infusions, Intravenous
  • Male
  • Rats
  • Rats, Wistar
  • Recurrence
  • Self Administration
  • Sex Factors
  • Substance-Related Disorders / physiopathology*


  • Cocaine