Estrogen and oxytocin involvement in social preference in male mice: a study using a novel long‐term social preference paradigm with aromatase, estrogen receptor‐α and estrogen receptor‐β, oxytocin, and oxytocin receptor knockout male mice

Abstract

Certain aspects of social behavior help animals make adaptive decisions during encounters with other animals. When mice choose to approach another conspecific, the motivation and preference behind the interaction is not well understood. Estrogen and oxytocin are known to influence a wide array of social behaviors, including social motivation and social preference. The present study investigated the effects of estrogen and oxytocin on social preference using aromatase (ArKO), estrogen receptor (ER) α (αERKO), ERβ (βERKO), oxytocin (OTKO), oxytocin receptor (OTRKO) knockout and their respective wild-type (WT) male mice. Mice were presented with gonadally-intact versus castrated male (IC), intact male versus ovariectomized female (IF), or intact male versus empty cage (IE) stimuli sets for 5 days. ArWT showed no preference for either stimuli in IC and IF and intact male preference in IE, but ArKO mice preferred a castrated male or an ovariectomized female, or had no preference for either stimulus in IC, IF and IE stimuli sets, respectively, suggesting reduced intact male preference. α and β WT mice preferred a castrated male, showed no preference, and preferred an intact male in IC, IF and IE, respectively. αERKO mice displayed similar modified social preference patterns as ArKO, whereas the social preference of βERKO mice remained similar to βWT. OTWT preferred a castrated male whereas OTKO, OTRWT and OTRKO mice failed to show any preference in IC and none showed preference for either stimuli in IF. Collectively, these findings suggest that estrogen regulates social preference in male mice and that impaired social preference in oxytocin-deficient mice may be due to severe deficits in social recognition.

Conditioned social preference and reward value of activating oxytocin‐receptor‐expressing ventral tegmental area neurons following repeated daily binge ethanol intake

“…CRISPR/Cas9 global knockout of OxTR in prairie voles decreases the ability to distinguish a novel mouse from a familiar mouse (Horie et al, 2019). In mice, both oxytocin and OxTR knockout impairs social preference and/or social memory (Ferguson et al, 2000;Tsuda et al, 2018). However, systemic injection of an OxTR antagonist does not affect social behavior with either novel or familiar same-sex mice (Haskal de la Zerda et al,…”

Neural and Hormonal Basis of Opposite-Sex Preference by Chemosensory Signals

“…Our study found that when the odors of castrated and gonadally intact males were simultaneously presented in the preference test, sexually active male rats preferred that of the castrated one [ 53 , 54 , 55 ]. We considered it unlikely that the lack of testosterone (T) due to castration may newly produce an attractant for males, but that the lack of T disinhibits the negative feedback of the hypothalamus-pituitary-gonadal (HPG) axis, resulting in increased circulating levels of gonadotropin-releasing hormone (GnRH) and gonadotropins, and consequently, that those became male incentive odors.…”

Neurobiological Aspects of Face Recognition: The Role of Oxytocin

“…CD38 -/- mice demonstrate abnormal social memory and OT administration rescues it (Jin et al, 2007). And impaired social preference in oxytocin deficient mice may be due to severe deficits in social recognition (Tsuda et al, 2018). …”