Effects of an estrogen receptor alpha agonist on agonistic behaviour in intact and gonadectomized male and female mice

Gonadal hormones mediate both affiliative and agonistic social interactions. Research in estrogen receptor alpha (ERα) or beta (ERβ) knockout (KO) mice suggests that ERα increases and ERβ decreases male aggression, while the opposite is found for female ERαKO and ERβKO mice. Using a detailed behavioural analysis of the resident-intruder test, we have shown that the ERβ selective agonist WAY-200070 increased agonistic behaviours, such as aggressive grooming and pushing down a gonadectomized (gonadex) intruder, in gonadally intact but not gonadex male and female resident mice, while leaving attacks unaffected. The role of acute activation of ERα in agonistic behaviour in adult non-KO CD1 mice is presently unknown. The current study assesses the effects of the ERα selective agonist 1,3,5-tris(4-hydroxyphenyl)-4-propyl-1H-pyrazole (PPT) on the social and agonistic responses of gonadally intact and gonadex male and female CD1 mice to a gonadex, same-sex intruder. PPT had few effects in gonadally intact mice, but seems to increase sex-typical aggression (i.e., attacks in males, other dominance-related behaviours in females) in gonadex mice. In untreated mice, we confirmed our previous findings that gonadally intact males attacked the intruder more than females, but females spent more time engaged in agonistic behaviour than males. As in our previous results, we observed that gonadex mice generally show behaviour patterns more like those of the gonadally intact opposite sex, while leaving overall levels of agonistic behaviour unaffected. Taken together, our current and previous results show that exogenous activation of ERα had no effects in gonadally intact mice, but increased sex-typical agonistic behaviour in gonadex mice, while ERβ had no effects in gonadex mice, but increased non-attack agonistic behaviour in gonadally intact animals. This suggests that, as in social recognition, ERα may be necessary for the activation of agonistic responses, while ERβ may play a modulatory role.