Acquisition of cocaine self-administration in ovariectomized female rats: effect of estradiol dose or chronic estradiol administration.
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.
Molecular and Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI 48109, United States.
Ming
M
Hu
Jill B
JB
Becker
D000818:Animals; D003042:Cocaine / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology*; D005260:Female; D015200:Fluoroimmunoassay; D010052:Ovariectomy / Q000706:statistics & numerical data*; D011597:Psychomotor Performance / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D012737:Sex Factors; D019966:Substance-Related Disorders / Q000453:epidemiology*
D004958:Estradiol; D003042:Cocaine