Glutamatergic systems play a critical role in the pathophysiology and treatment of stress-related disorders. In the present study, we conducted behavioral and neurochemical experiments to reveal involvement of glutamate receptors in the impairment of social behaviors induced by stress exposure as juveniles. Acute administration of ketamine, a non-competitive NMDA receptor antagonist and subsequent AMPA receptor stimulation attenuated the impairment of social behaviors in adolescent mice exposed to social defeat stress as juveniles. NBQX, a selective AMPA receptor antagonist prevented the attenuating effect of ketamine on the impairment of social behaviors. Although there were no significant changes in the ratios of phosphorylated protein of some NMDA subunits, that of AMPA receptor GluA1 subunit was significantly increased in the hippocampus of non-tested, defeated mice. In non-tested, defeated mice, ketamine increased the hippocampal total protein level, but not the ratio of phosphorylated protein of GluA1. These results suggest that exposure to social defeat stress as juveniles induces the impairment of social behaviors in adolescents through the functional changes in AMPA receptors.

To: 要旨(抄録)