Acquisition of cocaine self-administration in ovariectomized female rats: effect of estradiol dose or chronic estradiol administration

Drug Alcohol Depend. 2008 Apr 1;94(1-3):56-62. doi: 10.1016/j.drugalcdep.2007.10.005. Epub 2007 Dec 3.


This study was conducted to investigate whether the dose of estradiol (E) administered acutely, or chronic delivery of one dose of E impacts acquisition and subsequent cocaine self-administration in ovariectomized (OVX) female rats. Five groups of female rats were compared: OVX females treated with 0, 1, 2, or 5 microg 17beta-E, 30 min prior to the self-administration session, and OVX rats that received a 1.5mg E pellet (designed to chronically release 25 microg E/day X 60 days) implanted 1 week before cocaine self-administration initiation. Rats were tested in 1h sessions on a FR1 schedule with the dose of cocaine increasing every week (testing occurred 5 day/week; doses: 0.2, 0.3, 0.4, 0.5 and 0.75 mg/(kg infusion)). We report that OVX rats treated with 2 microg E acquired self-administration more rapidly than all of the other groups, and animals that received 1 or 2 microg E self-administered significantly more cocaine compared to OVX+vehicle at 0.3 and 0.4 mg/(kg infusion). In contrast, OVX rats given 5 microg E acutely, or chronic E via slow-release pellets did not take more cocaine than the OVX+vehicle group at any time point. Physiological serum concentrations of E were seen with 1 or 2 microg E, but 5 microg E and the E pellet produced supra-physiological concentrations. These results suggest an inverted U-shaped dose-response curve for the effect of E on acquisition of cocaine self-administration.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cocaine / administration & dosage*
  • Drug Administration Schedule
  • Estradiol / administration & dosage*
  • Estradiol / pharmacology*
  • Female
  • Fluoroimmunoassay
  • Ovariectomy / statistics & numerical data*
  • Psychomotor Performance / drug effects*
  • Rats
  • Rats, Sprague-Dawley
  • Self Administration*
  • Sex Factors
  • Substance-Related Disorders / epidemiology*


  • Estradiol
  • Cocaine