Impaired sex preference, but not social and social novelty preferences, following systemic blockade of oxytocin receptors in adult male mice

Abstract The hypothalamic neuropeptide oxytocin (OT) is a powerful modulator of mammalian social behavior and its administration was shown to affect various types of social interactions. However, systematic examinations of the role of endogenous OT release in social behavior have heretofore been done only using genetically modified animal models in which the genes encoding either OT or the OT receptor (OTR) were mutated. While such genetic manipulations revealed various behavioral deficits, these deficits may involve developmental or long-term processes and do not prove the participation of acute OT release in the impaired behavior. Here we used a battery of social discrimination tasks to evaluate the effects of acute systemic OTR blockade, using a non-peptide, orally active OTR antagonist (L368,899), on social behavior of adult male C57BL/6 J mice. We found no effect of the pharmacological manipulation on the social preference and social novelty preference behaviors. However, the preference of a male mouse for investigating a female conspecific more than a male (sex preference behavior), was lost by administration of the OTR antagonist. Finally, we found that blocking OTR activity before social defeat prevented the consequent loss of social preference, suggesting a role for OT in the acquisition of aversive social memory. Overall, our results suggest that OT plays a role in modulating the salience of social stimuli and facilitating their memory, as predicted by the social salience theory, rather than in regulating the internal motivation of the subject for social interactions.