Estrogen receptors alpha and beta mediate different aspects of the facilitatory effects of female cues on male risk taking.

Male risk taking and decision making are affected by sex-related cues, with men making poorer and riskier decisions in the presence of females and, or their cues. In non-human species, female cues can also increase male risk taking, reducing their responses to predator threat. As estrogen receptors alpha and beta (ERalpha and ERbeta) are involved in the mediation of social and sexual responses, we investigated their roles in determining the effects of female-associated cues on male risk taking. We examined the effects of brief pre-exposure to the odors of either a novel or familiar estrous female on the avoidance of, and aversive responses to, predator threat (cat odor) in ERalpha and ERbeta wild type (alphaERWT, betaERWT) and gene-deleted (knockout, alphaERKO, betaERKO) male mice. Exposure of alphaERWT and betaERWT males to the odors of a novel, but not a familiar, estrous female mouse resulted in enhanced risk taking with the males displaying reduced avoidance of, and analgesic responses to, cat odor. In contrast, alphaERKO male mice failed to show any changes in risk taking, while betaERKO males, although displaying greater risk taking, did not distinguish between novel and familiar females, displaying similarly reduced avoidance responses to cat odor after exposure to either a novel or familiar female odor. These findings indicate that the gene for ERalpha is associated with the sexual mechanisms (response to estrous female) and the genes for ERbeta and ERalpha with the social (recognition of novel female) mechanisms underlying the effects of female cues on male risk taking.