Involvement of Serotonin and Oxytocin in Neural Mechanism Regulating Amicable Social Signal in Male Mice: Implication for Impaired Recognition of Amicable Cues in BALB/c Strain

Social signals play a primary role in regulating social relationships among male mice. The present series of experiments investigated the neural mechanisms underlying an induction of amicable cues that facilitate social approach in male mice of the C57BL/6 (B6) and BALB/c (BALB) strains. Male mice exhibit approach behavior and suppression of territorial scent marking toward amicable counterparts. Exposure of a group-housed mouse that maintains an amicable relationship induced social approach in B6 recipient mice, as expressed by increased preference of stay in proximity and decreased scent marks relevant to those of a single-housed mouse. Nasal administration of oxytocin (OT) to stimulus mice appeared to enhance social approach in B6 recipient mice. Systemic administration of buspirone (5-HT1A agonist) to stimulus mice also increased approach in B6 recipient mice, whereas a nasal OT antagonist infusion followed by systemic buspirone injection of stimulus mice blocked this buspirone-induced approach in B6 recipient mice. BALB mice likely possess an intact signaling system as shown in B6 mice, in which the 5-HT -> OT pathway is a primary modulator for social amicable signals. However, BALB mice could not exhibit signal-dependent change in approach behavior. No impairment in olfactory discrimination or approach behavior toward social stimuli was found in BALB mice. It is concluded that social cues for facilitating social approach are eliminated via the 5-HT -> OT pathway, and BALB mice as a low social strain have a deficit in recognition of specific signals associated with amicability.