Oxytocin receptor knockout mice display deficits in the expression of autism-related behaviors

Abstract

A wealth of studies has implicated oxytocin (Oxt) and its receptors (Oxtr) in the mediation of social behaviors and social memory in rodents. It has been suggested that failures in this system contribute to deficits in social interaction that characterize autism spectrum disorders (ASD). In the current analyses, we investigated the expression of autism-related behaviors in mice that lack the ability to synthesize the oxytocin receptor itself, Oxtr knockout (KO) mice, as compared to their wild-type (WT) littermates. In the visible burrow system, Oxtr KO mice showed robust reductions in frontal approach, huddling, allo-grooming, and flight, with more time spent alone, and in self-grooming, as compared to WT. These results were corroborated in the three-chambered test: unlike WT, Oxtr KO mice failed to spend more time in the side of the test box containing an unfamiliar CD-1 mouse. In the social proximity test, Oxtr KO mice showed clear reductions in nose to nose and anogenital sniff behaviors oriented to an unfamiliar C57BL/6J (B6) mouse. In addition, our study revealed no differences between Oxtr WT and KO genotypes in the occurrence of motor and cognitive stereotyped behaviors. A significant genotype effect was found in the scent marking analysis, with Oxtr KO mice showing a decreased number of scent marks, as compared to WT. Overall, the present data indicate that the profile for Oxtr KO mice, including consistent social deficits, and reduced levels of communication, models multiple components of the ASD phenotype. This article is part of a Special Issue entitled Oxytocin, Vasopressin, and Social Behavior.

Fig. 1

Individual frequencies (mean ± S.E.M.) of approaches to the front (A), approaches to the back (B), flight (C), and chase/follow (D) behaviors of WT and Oxtr KO mice during the dark and light periods in the VBS; n = 12 for each group; *p < 0.05 compared to WT by unpaired t-test.

Fig. 2

Individual frequencies (mean ± S.E.M.) of self-grooming (A), and allo-grooming (B), and percentage of observations (mean ± S.E.M.) of huddling behavior (C) or being alone (D) of WT and Oxtr KO mice during the dark and light periods in the VBS; n = 12 for each group; *p < 0.05 compared to WT by unpaired t-test.

Fig. 3

Time spent in each side (mean ± S.E.M.) during the three-chambered social approach test. *p < 0.05, within-genotype comparison; n = 13 for WT and 16 for Oxtr KO.

Fig. 4

Frequency (mean ± S.E.M.) of variables assessed in the self-grooming analysis; n = 13 for WT and 16 for Oxtr KO.

Fig. 5

Frequency (mean ± S.E.M.) of social behaviors obtained when Oxtr WT and KO mice were confined with an unfamiliar B6 mouse in the social proximity chamber; n = 13 for WT and 16 for Oxtr KO; *p < 0.05 compared to WT by unpaired t-test.

Fig. 6

Frequency (mean ± S.E.M.) of variables assessed in the repetitive novel object contact task; n = 13 for WT and 16 for Oxtr KO.