Oxytocin and estrogen receptor alpha and beta knockout mice provide discriminably different odor cues in behavioral assays

Social behavior involves both the recognition and production of social cues. Mice with selective deletion (knockout) of either the gene for oxytocin (OT) or genes for the estrogen receptor (ER) -α or -β display impaired social recognition. In this study we demonstrate that these gene knockout mice also provide discriminably different social stimuli in behavioral assays. In an odor choice test, which is a measure of social interest and discrimination, outbred female Swiss-Webster mice discriminated the urine odors of male knockouts (KO: OTKO, αERKO, βERKO) from the odors of their wildtype littermates (WT: OTWT, αERWT, βERWT). Females showed marked initial choices of the urine odors of OTWT and βERWT males over those of OTKO and βERKO males, and αERKO males over αERWT males. The odors of OTKO and βERKO males also induced aversive, analgesic responses, with the odors of WTs having no significant effects. Odors of both the αERWT and αERKO males induced aversive, analgesic responses, with the odors of the WT inducing significantly greater analgesia. The odors of restraint stressed WT and KO males also elicited analgesia with, again, females displaying significantly greater responses to the odors of stressed OTKO and βERKO males than their WTs, and significantly lower analgesia to the odors of stressed αERKO than αERWT males. These findings show that the KO mice are discriminated from their WTs on the basis of odor and that the various KOs differ in the relative attractiveness/aversiveness of their odors. Therefore, in behavioral assays one causal route by which gene inactivation alters the social behavior of knockout mice may be mediated through the partners' modified responses to their odors.