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

The neurosteroid dehydroepiandrosterone (DHEA) is a powerful inhibitor of a ggression in murine models when given for 15 days and potentially may be us eful in the management of inappropriate human aggression, Although the bios ynthesis and metabolism of DHEA have been described, little is known about the potential effect of the steroidal environment during sexual differentia tion on the subsequent response to DHEA, Whether prenatal androgen exposure influences the subsequent response to DHEA was assessed by comparing the e ffect of DHEA (80 mug/d) on aggression in female offspring where darns were treated with 1, 10, or 100 mug of testosterone (T) on days 15 to 18 of ges tation (Experiment T) or that developed in different uterine positions (Exp eriment II), The results shelved that DHEA decreased attack behavior in gen eral and that the 100-mug prenatal T treatments enhanced the antiaggressive effect of this neurosteroid, Neither the lower doses of exogenously admini stered T nor the uterine position led to an enhanced response to DHEA, In a ddition, whether DHEA produced changes in social and nonsocial activities w as examined. In the 100-mug T females, DHEA increased the duration of the f ormer and decreased the frequency and duration of the latter, indicating th at it was not a general decrement in behavioral expression that mediated th e enhanced response to the antiaggressive effect of DHEA, In the second exp eriment, DHEA treatment led to increased frequencies of social nonaggressiv e and nonsocial activities. However, the uterine positions x treatment inte ractions were not significant, demonstrating that contiguity to male fetuse s did not differentially affect the response to DHEA. (C) 2001 Wiley-Liss, Inc.