Abstract
The role of sex and androgen receptors (ARs) for social preference and social memory is rather unknown. In this study of mice we compared males, females and males lacking ARs specifically in the nervous system, ARNesDel, with respect to social preference, assessed with the three-chambered apparatus test, and social recognition, assessed with the social discrimination procedure. In the social discrimination test we also evaluated the tentative importance of the sex of the stimulus animal. Novel object recognition and olfaction were investigated to complement the results from the social tests. Gene expression analysis was performed to reveal molecules involved in the effects of sex and androgens on social behaviors. All three test groups showed social preference in the three-chambered apparatus test. In both social tests an AR-independent sexual dimorphism was seen in the persistence of social investigation of female conspecifics, whereas the social interest toward male stimuli mice was similar in all groups. Male and female controls recognized conspecifics independent of their sex, whereas ARNesDel males recognized female but not male stimuli mice. Moreover, the non-social behaviors were not affected by AR deficiency. The gene expression analyses of hypothalamus and amygdala indicated that Oxtr, Cd38, Esr1, Cyp19a1, Ucn3, Crh, and Gtf2i were differentially expressed between the three groups. In conclusion, our results suggest that ARs are required for recognition of male but not female conspecifics, while being dispensable for social investigation toward both sexes. In addition, the AR seems to regulate genes related to oxytocin, estrogen and William’s syndrome.
Highlights
It is well established that testosterone is crucial for sexual dimorphisms in rodents as well as other vertebrates regarding social behaviors, such as aggression, mating behaviors and parental care
Male ARNesDel mice, as well as male and female control mice, were investigated in the three-chambered apparatus in order to determine if sex and/or presence of androgen receptors (ARs) in the nervous system influenced the sociability (Figure 1)
In contrast to male and female siblings, the ARNesDel males lacked social memory when presented to male conspecifics, while all three groups displayed social preference and social memory when presented to female stimuli animals
Summary
It is well established that testosterone is crucial for sexual dimorphisms in rodents as well as other vertebrates regarding social behaviors, such as aggression, mating behaviors and parental care. The behavioral effects of testosterone are mediated by actions of androgen receptors (ARs), and after aromatization of testosterone to 17-beta-estradiol, by estrogen receptors (ERs). These receptors are expressed in specific nuclei of the hypothalamus, amygdala and related regions. Androgen Receptors in Social Recognition rodents lacking either their gonads, ARs or ERs display substantially decreased aggression and sexual behaviors (Ogawa et al, 1997; Sato et al, 2004; Pfaff et al, 2005; Zuloaga et al, 2008b; Raskin et al, 2009, 2012; Juntti et al, 2010; Marie-Luce et al, 2013; Studer et al, 2015). The knowledge about the role of brain ARs for social investigation, social preference and social recognition is, remarkably sparse
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