Journal of pharmacological sciences
March 1, 2025
Mikio Yoshida, Hikari Katada, Yuya Isozumi et al.
4 citations
In mice exposed to social defeat stress as juveniles, social behavior impairments were linked to elevated levels of GluN2C and GluN2D proteins in the prefrontal cortex. Acute administration of PPDA, a GluN2C/GluN2D antagonist, or ketamine, a non-competitive NMDA receptor antagonist, reduced these impairments. The effect of ketamine was partially blocked by CIQ, a GluN2C/GluN2D potentiator. Activation of GluN2C- and/or GluN2D-containing NMDA receptors appears to contribute to social behavior deficits from juvenile stress, and these subunits may be involved in ketamine's therapeutic action. Targeting these subunits could offer new treatment strategies for stress-related psychiatric disorders in adolescents.
Neurochemistry international
January 1, 2007
Akihiro Mouri, Yukihiro Noda, Takeshi Enomoto et al.
Phencyclidine (PCP), a drug that blocks NMDA receptors, produces schizophrenia-like symptoms in humans, including positive symptoms, negative symptoms, and cognitive problems. This supports the glutamatergic dysfunction hypothesis of schizophrenia. Adult rodents given repeated PCP show hyperlocomotion (positive symptoms), social deficits, increased immobility (negative symptoms), sensorimotor gating problems, and cognitive impairments; some changes persist after withdrawal. Repeated PCP also causes neurochemical and neuroanatomical changes. Exposure to viral or environmental insults during the second trimester of pregnancy raises schizophrenia risk. Perinatal PCP treatment impairs neuronal development and leads to long-lasting schizophrenia-like behaviors in adulthood. These animal models are useful for testing treatments and studying schizophrenia's mechanisms.
Annals of the New York Academy of Sciences
November 1, 2006
Toshitaka Nabeshima, Akihiro Mouri, Rina Murai et al.
Repeated administration of phencyclidine (PCP) to mice produces behavioral deficits resembling the negative symptoms and cognitive impairments of schizophrenia, including increased immobility in a forced swimming test and impaired latent learning. These deficits persist after PCP withdrawal and are alleviated by atypical but not typical antipsychotics. PCP treatment reduces spontaneous glutamate levels and impairs NMDA receptor function in the prefrontal cortex, disrupting both pre- and postsynaptic glutamate transmission. Facilitation of NMDA receptor function with glycine-site agonists like D-cycloserine or glycine reverses the abnormal intracellular signaling and behavioral deficits. The findings suggest that disrupted NMDA receptor signaling underlies the emotional and cognitive deficits in this mouse model, which may be useful for studying antipsychotic effects.
ChemInform
November 28, 2000
Yukihiro Noda, Toshitaka Nabeshima
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