Male risk taking, female odors, and the role of estrogen receptors

Abstract

Male risk-taking and decision making are affected by sex-related cues, with men making riskier choices and decisions after exposure to either women or stimuli associated with women. In non-human species females and, or their cues can also increase male risk taking. Under the ecologically relevant condition of predation threat, brief exposure of male mice to the odors of a sexually receptive novel female reduces the avoidance of, and aversive responses to, a predator. We briefly review evidence showing that estrogen receptors (ERs), ERα and ERβ, are associated with the mediation of these risk taking responses. We show that ERs influence the production of the female odors that affect male risk taking, with the odors of wild type (ERαWT, ERβWT), oxytocin (OT) wildtype (OTWT), gene-deleted 'knock-out' ERβ (ERβKO), but not ERαKO or oxytocin (OT) OTKO or ovariectomized (OVX) female mice reducing the avoidance responses of male mice to cat odor. We further show that administration of specific ERα and ERβ agonists to OVX females results in their odors increasing male risk taking and boldness towards a predator. We also review evidence that ERs are involved in the mediation of the responses of males to female cues, with ERα being associated with the sexual and both ERβ and ERα with the sexual and social mechanisms underlying the effects of female cues on male risk taking. The implications and relations of these findings with rodents to ERs and the regulation of human risk taking are briefly considered.

Fig. 1

Effects of a 1 min pre-exposure to the urine and bedding odors of a novel sexually receptive female on the subsequent responses of sexually naïve male mice in a Y-maze odor preference apparatus to a predator (cat odor) and non-predator (novel odor, almond), odor combination. Male mice were pre-exposed to the odors of either: an intact adult sexually receptive CD-1 female (intact female), an ovariectomized female (OVX) or an ERαWT, ERαKO, ERβWT, ERβKO, OTKO, or OTWT female. The responses of mice receiving no prior odor exposures (no female, control) are also shown. Responses are given as preference ratios (e.g. time spent in the vicinity of the predator odor/time spent in the vicinity of the predator odor+time spent in the vicinity of the non-predator odor). Preferences were determined over a 5 min time period. Increased preference indicates an augmented interest in, and approach to, the predator odor and is indicative of a reduced avoidance of the predator odor. Stars (*) indicate significant (p<0.05) increases in risk taking and reduced avoidance of predator odor. N=10, in all cases. Vertical lines denote a standard error of the mean.

Fig. 2

Nociceptive responses of adult sexually naïve male mice that were pre-exposed for 1 min to the urine odors of either a sexually receptive intact CD-1-female (intact female) or an ovariectomized female (OVX) and then exposed for 1 min to predator (cat) odor. Responses of mice receiving no female odor exposure (no female) are also given. Nociceptive sensitivity, as measured by the latency of response to a 50 °C thermal surface, was determined before any odor exposures (baseline), after exposure to a female (post-female) and after exposure to the predator odor (post-predator). Stars (*) indicate a significant (p<0.05) decrease in predator odor induced analgesia. N=10 in all cases. Vertical lines denote a standard error of the mean.

Fig. 3

Effects of a 1 min pre-exposure to the urine and bedding odors of a novel female on the subsequent responses of male mice in a Y-maze odor preference apparatus to a predator (cat odor) and non-predator (novel odor, almond), odor combination. Male mice were pre-exposed to the odors of either: a sexually receptive intact CD-1 female (intact female), an ovariectomized female (OVX), or an ovariectomized female treated with either an ERβ agonist (WAY-200070, 30 mg/kg, 72 h prior) (OVX+ERβ), ERα agonist (PPT, 0.10 mg/kg, 72 h prior) (OVX+ERα) or the vehicle (Veh, sesame oil, 10 ml/kg, 72 h prior). The responses of mice receiving no prior odor exposures (no female, control) are also shown. Responses are given as preference ratios (e.g. time spent in the vicinity of the predator odor/time spent in the vicinity of the predator odor+time spent in the vicinity of the non-predator odor). Preferences were determined over a 5 min time period. Increased preference indicates an augmented interest in, and approach to, the predator odor and is indicative of a reduced avoidance of the predator odor. Stars (*) indicate significant (p<0.05) increases in risk taking and reduced avoidance of predator odor. N=10, in all cases. Vertical lines denote a standard error of the mean.

Fig. 4

Nociceptive responses of adult sexually naïve male mice that were pre-exposed for either 1 min to the urine odors of either a sexually receptive intact CD-1 female (intact female), an ovariectomized female (OVX), or an ovariectomized female treated with either an ERβ agonist (WAY-200070, 30, 90 mg/kg, 72 h prior) (OVX+ERβ) or the vehicle (sesame oil, 10 ml/kg, 72 h prior) and then exposed for 1 min to predator (cat) odor. Nociceptive sensitivity, as measured by the latency of response to a 50 °C thermal surface, was determined before any odor exposures (baseline), after exposure to a female odor (post-female) and after exposure to the predator odor (post-predator). Stars (*) indicate a significant (p<0.05) decrease in predator odor induced analgesia N=10, in all cases. Vertical lines denote a standard error of the mean. N=10, in all cases.