Agonistic behavior in males and females: effects of an estrogen receptor beta agonist in gonadectomized and gonadally intact mice.

Affiliative and agonistic social interactions are mediated by gonadal hormones. Research with estrogen receptor alpha (ERalpha) or beta (ERbeta) knockout (KO) mice show that long-term inactivation of ERalpha decreases, while inactivation of ERbeta increases, male aggression. Opposite effects were found in female alphaERKO and betaERKO mice. The role of acute activation of ERalpha or ERbeta in the agonistic responses of adult non-KO mice is unknown. We report here the effects of the ERbeta selective agonist WAY-200070 on agonistic and social behavior in gonadally intact and gonadectomized (gonadex) male and female CD-1 mice towards a gonadex, same-sex intruder. All 15min resident-intruder tests were videotaped for comprehensive behavioral analysis. Separate analyses assessed: (1) effects of WAY-200070 on each sex and gonadal condition; (2) differences between sexes, and between gonadally intact and gonadex mice, in untreated animals. Results show that in gonadally intact male and female mice, WAY-200070 increased agonistic behaviors such as pushing down the intruder and aggressive grooming, while leaving attacks unaffected. In untreated mice, males attacked more than females, and gonadex animals showed less agonistic behavior than same-sex, gonadally intact mice. Overall, our detailed behavioral analysis suggested that in gonadally intact male and female mice, ERbeta mediates patterns of agonistic behavior that are not directly involved in attacks. This suggests that specific aspects of aggressive behavior are acutely mediated by ERbeta in adult mice. Our results also showed that, in resident-intruder tests, female mice spend as much time in intrasexual agonistic interactions as males, but use agonistic behaviors that involve extremely low levels of direct attacks. This non-attack aggression in females is increased by acute activation of ERbeta. Thus, acute activation of ERbeta similarly mediates agonistic behavior in adult male and female CD-1 mice.