Sex Differences in Social Investigation: Effects of Androgen Receptors, Hormones and Test Partner

We examined the role of the androgen receptor (AR) in the investigatory behaviour of conspecifics using mice carrying the testicular feminisation mutation (XTfmY). Responses to members of the same and opposite sex were evaluated in a habituation/dishabituation task. Adult mice were gonadectomised and treated with oestradiol (E2) or testosterone. After E2 treatment, regardless of the sex of the stimulus mouse, wild-type (WT) males engaged in significantly more investigation than WT females. XTfmY males treated with E2 showed male-like behaviour in response to a male but behaved female-like when the stimulus was a female. Because WT and XTfmY males behaved the same in response to another male, we used two additional mouse models to ask whether sex chromosomes were responsible for this phenomenon. Regardless of sex chromosome complement, gonadal males displayed high levels of investigation. When mice were treated with testosterone, investigation by WT females was enhanced, which eliminated the sex differences. Most strikingly, XTfmY males receiving testosterone-treatment increased the investigation of females to levels equal to those shown by WT mice. Given that testosterone, but not its metabolite E2, caused XTfmY males to investigate female conspecifics at high levels, it is plausible that nonclassical actions of AR, and/or activation of a novel AR, may be involved in this behaviour. Taken together, our data show that AR activation during adulthood is not required for males to investigate mice of either sex. However, male-like levels of investigation of a female stimulus may depend on neonatal activation of the classic nuclear AR.