Prenatal testosterone treatment potentiates the aggression‐inhibiting effect of the neurosteroid dehydroepiandrosterone in female mice

The neurosteroid dehydroepiandrosterone (DHEA) is a powerful inhibitor of aggression in murine models when given for 15 days and potentially may be useful in the management of inappropriate human aggression. Although the biosynthesis and metabolism of DHEA have been described, little is known about the potential effect of the steroidal environment during sexual differentiation on the subsequent response to DHEA. Whether prenatal androgen exposure influences the subsequent response to DHEA was assessed by comparing the effect of DHEA (80 μg/d) on aggression in female offspring where dams were treated with 1, 10, or 100 μg of testosterone (T) on days 15 to 18 of gestation (Experiment I) or that developed in different uterine positions (Experiment II). The results showed that DHEA decreased attack behavior in general and that the 100‐μg prenatal T treatments enhanced the antiaggressive effect of this neurosteroid. Neither the lower doses of exogenously administered T nor the uterine position led to an enhanced response to DHEA. In addition, whether DHEA produced changes in social and nonsocial activities was examined. In the 100‐μg T females, DHEA increased the duration of the former and decreased the frequency and duration of the latter, indicating that it was not a general decrement in behavioral expression that mediated the enhanced response to the antiaggressive effect of DHEA. In the second experiment, DHEA treatment led to increased frequencies of social nonaggressive and nonsocial activities. However, the uterine positions × treatment interactions were not significant, demonstrating that contiguity to male fetuses did not differentially affect the response to DHEA. Aggr. Behav. 27:130–138, 2001. © 2001 Wiley‐Liss, Inc.