Acute estradiol treatment affects the expression of cocaine-induced conditioned place preference in ovariectomized female rats.

Abstract Women and female rodents are more responsive to the subjective effects of psychostimulant drugs of abuse compared to males. A growing body of literature supports a role for estradiol as a mechanism underlying these sex differences. However, little is known about the influence of acute elevations in levels of estradiol on drug conditioned behaviors. The aim of the present study was to evaluate the influence of an acute increase in systemic estradiol levels on the expression of cocaine conditioned place preference (CPP). Using a six day conditioning procedure, ovariectomized (OVX) female rats were conditioned with one of four doses of cocaine (2.5, 5, 10, or 15 mg/kg) to associate one of two large chambers of a CPP apparatus with cocaine or saline. Thirty minutes prior to the start of the CPP preference test, rats were pretreated with either 5 μg estradiol benzoate (EB) or peanut oil (PO). PO-treated rats expressed a significant preference for only the mid-range conditioning doses of cocaine (5 and 10 mg/kg). However, acute EB treatment resulted in a rightward shift in the cocaine dose–response curve; rats demonstrated a significant preference at only the moderate and high conditioning doses of cocaine (10 and 15 mg/kg). These findings demonstrate that acute elevations in estradiol may dampen the expression of conditioned responses to cocaine's secondary rewards at lower conditioning doses of the drug and facilitate CPP at higher doses while estradiol deficiency decreases the threshold dose of cocaine necessary to induce CPP.