Testosterone, but not estradiol, dictates the expression of conditioned place preference for sexual behavior in male rats.

Background: Although treatment with testosterone, or in some cases estradiol, reverses deficits in sexual motivation induced by the suppression of gonadal hormone signaling, the effects of testosterone or estradiol treatment on the expression of sexual reward remain to be determined.

Aim: The aims of the study were to (1) determine if testosterone was critical for the expression of conditioned place preference (CPP) induced by sexual activity (ie, expression of sexual reward) and (2) if the effects of testosterone treatment on the expression of sexual reward could be mimicked by treatment with estradiol alone.

Outcomes: The percentage of time spent in the chamber of a CPP apparatus associated with sexual activity was indicative of the expression of sexual reward, while the relative weights of the seminal vesicles and changes in body weight were analyzed to characterize androgen and estrogen activity, respectively.

Methods: All sexually experienced Long-Evans male rats were first treated with a long-acting gonadotropin-releasing hormone receptor antagonist following their final conditioning trial, in which they learned to associate one end chamber of a 3-chambered CPP apparatus with sexual activity. Males were then treated with oil or single doses of either testosterone or estradiol 96 and 48 h prior to their CPP test trials and removal of seminal vesicles.

Results: Only males treated with testosterone expressed CPP induced by sexual activity. Additionally, testosterone-treated males spent a significantly greater percentage of time in the chamber of the CPP apparatus associated with sexual activity than estradiol-treated males, an effect that also tended to be the case when comparing testosterone to oil-treated males. Testosterone increased the relative weight of the seminal vesicles, and estradiol treatment resulted in weight loss.

Clinical implications: Although testosterone treatment impacted the expression of sexual reward, the results also suggest that treatment with estradiol alone may have limited clinical utility for treating those who are hypogonadal or undergoing androgen deprivation therapies, as the hormone did not mimic the effect of testosterone on the expression of sexual reward.

Strengths and limitations: Strengths include the experimental nature of the study and novel investigation into the effect of testosterone and estradiol on the expression of sexual reward. Although the hormone was bioactive, one limitation of the study was the use of a single dose of estradiol.

Conclusion: Treatment with testosterone, but not estradiol alone, regulates the expression of sexual reward in male rats.