Disruption of ultrasonic vocalization with systemic administration of the non-competitive N-methyl-d-aspartate receptor antagonist MK-801 in adult male mice

Vocal communication is essential for survival in many animals, including humans. Mice produce ultrasonic vocalizations (USVs) in various social contexts. N-methyl-d-aspartate (NMDA) receptors are widely distributed in the central nervous system and play essential roles in synaptic plasticity, learning, and behavior. However, the role of NMDA receptors in USVs remains unclear. Here, we examined the effects of systemic administration of a noncompetitive NMDA antagonist, MK-801, on USVs during courtship and in other social and nonsocial behaviors. First, we investigated the USVs emitted by male mice. After the successful classification of USVs into 11 categories using VocalMat, an open-source computational vision and machine-learning technique, we analyzed the relationship between USV properties and approaching behavior toward female mice. Male mice produced USVs when they were close to female mice, which confirmed that USVs were associated with social signals. Second, we examined the effects of intraperitoneal injection of MK-801 on USVs and approach behavior. Intraperitoneal injection of MK-801 dose-dependently decreased the number of USVs and increased locomotor activity, but did not affect the time spent with female mice. In additional experiments, we confirmed that the injection of MK- 801 decreased the time spent with a novel same-sex individual in the social preference task, increased locomotor activity, and inhibited excretion in the open-field task. Taken together, these results demonstrate that NMDA receptors play important roles in vocal communication and social behavior.