Estrogen receptors α and β mediate different aspects of the facilitatory effects of female cues on male risk taking
Introduction
Sex-related cues have a significant impact on male behavior. Men are reported to make “poorer” and riskier decisions when female-related cues are present (Roney et al., 2003, Roney et al., 2007; Wilson and Daly, 2004; Ariely and Lowenstein, 2006; Van den Bergh and Dewitte, 2006). In non-humans, predation threat provides an ethologically relevant risk for examining male decision taking (Lima and Dill, 1990; Kavaliers and Choleris, 2001). For example, the presence of a female leads to a greater risk taking and boldness by male guppies towards a predator (Godin and Dugatkin, 1996).
Animals generally respond to the threat of predation risk with a number of defensive behaviors including either immobilization or fleeing, an increase in corticosterone levels, as well as a decrease in nociceptive sensitivity and the induction of analgesia (Blanchard et al., 1990, Blanchard et al., 1998; Kavaliers and Colwell, 1991; Kavaliers and Choleris, 2001). In rodents, where chemical signals play a key role in social behavior and communication (e.g. Hurst and Benyon, 2004; Hurst et al., 2001; Beynon and Hurst, 2003), male mice that are exposed to female odor show reduced fear responses and greater risk taking. Brief exposure to the urinary odors of a novel, though not a familiar, estrous female, enhances the risk taking and boldness displayed by male mice reducing their avoidance of predator odor as well as the predator-induced rises in corticosterone and analgesic responses (Kavaliers et al., 2001).
This risk-enhancing phenomenon is, thus, composed of two aspects. One is a sexual component involving a response to a sexually receptive female and her cues, while the other consists of a social response involving the distinction between a novel and familiar individual. Only a novel estrous female will induce this enhanced risk taking by a male. These sexual and social components allow males to selectively respond to sexually receptive and potentially accessible novel females, thereby, potentially increasing their reproductive fitness.
The neurobiological mechanisms that underlie social and sexual behaviors and responses (e.g. Choleris et al., 2003, Choleris et al., 2004; Insel and Fernald, 2004; Keverne and Curley, 2004) as well as those that affect risk taking and boldness (e.g. Montague and Berns, 2002; Trepel et al., 2005; Ditto et al., 2006) are coming under increased scrutiny. There is mounting evidence that estrogens and estrogen receptors (ERs) have an important role in determining various aspects of social and sexual behavior in males as well as in females. Mice in which the genes encoding either estrogen receptor α (ERα) or estrogen receptor β (ERβ) had been disrupted (ER-knockout mice (ERKO, αERKO, βERKO)) were impaired in their olfactory-mediated social recognition (Imwalle et al., 2002; Choleris et al., 2003, Choleris et al., 2006; Kavaliers et al., 2004). In addition, ERα has been associated with the mediation of male aggression and sexual behavior. ERα wild-type (αERWT) male mice displayed normal sexual behavior and mating with estrous females while αERKO males failed to do so. αERKO males were, however, reported to show normal responses to, and interests in, the odors of estrous females (Ogawa et al., 1998, Ogawa et al., 2000, Ogawa et al., 2002; see, however, Rissman et al., 1999; Wersinger and Rissman, 2000). In contrast to ERα, the lack of a functional ERβ, while affecting social recognition (Choleris et al., 2003), did not impair normal expression of adult sexual behavior or preferences for females by male mice. Both the wild-type (βERWT) and βERKO male mice expressed an interest in, and responses to, female olfactory cues and exhibited normal sexual behavior, with the βERKO mice also displaying enhanced inter-male aggression (Ogawa et al., 1999, Ogawa et al., 2000; Nomura et al., 2002). Thus, ERα seems to be involved in the mediation of both social responses and sexual behaviors, while ERβ seems to be involved with social responses but not sexual behaviors. These findings raise the possibility that the genes for ERα and ERβ may also be differentially involved in mediating the sexual and social components of the impact of female cues on male risk-related behaviors. Here we examined the effects of brief exposure to the odors of either a novel or a familiar female on the subsequent avoidance and aversive responses of αERWT, βERWT, αERKO and βERKO male mice to predator odor.
Section snippets
Animals
Gonadally intact male αERKO and βERKO mice and their wild-type (WT) littermates (αERWT and βERWT); 25–30 g; 7–12 months of age) were used. They were obtained from the breeding colony maintained at The Rockefeller University (New York, NY, USA) by mating heterozygous male and female mice. The genotype of each mouse was determined by PCR amplification of tail DNA. Both colonies of mice were developed in a mixed 129/SvJ and C57BL/6J background and back-crossed into C57BL/6J. The original breeding
Experiment 1. Predator odor avoidance
All of the male mice displayed a similar marked overall preference for non-predator odor and avoidance of the predator odor when presented with the predator (cat odor) and non-predator (control odor) stimulus odor combination, with only 15–22% of their time being spent in the arm holding the predator odor (Figure 1A, B). This relative preference for non-predator odor and avoidance of predator odor was affected by pre-exposure to estrous female odor with a significant main effect of female odor
Discussion
Here we show that the genes for ERα and ERβ are differentially involved in mediating the facilitatory effects of female cues on risk taking by males. Male mice are “emboldened” in their responses to a predator after brief exposure to the odors of a novel female with the gene for ERα associated with the sexual mechanisms (response to estrous female) and the genes for ERβ, and likely ERα, with the social (recognition of a novel female) mechanisms of this effect. As “sex-related cues” have a
Roles of the funding sources
This study has been supported by the Natural Sciences and Engineering Research Council of Canada RO557A01(MK), 045881 (EC), NIH MH36273 (DWD), and NIMH 62147 (SO).
Conflict of interest statement
Jan-Ake Gustafsson is a shareholder, research grant receiver and consultant of KaroBio AB.
Acknowledgments
Supported by the Natural Sciences and Engineering Research Council of Canada (MK, EC), NIH MH36273 (DWD) and NIMH 62147 (SO).
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2012, Frontiers in NeuroendocrinologyCitation Excerpt :The enhanced risk taking seen in a male after exposure to female cues incorporates two aspects. One is a sexual component involving a response to a sexually receptive female, while the other is a social recognition element involving the distinction between a novel and familiar female [154,166]. Estrogens and ERs are involved in both of these aspects.