Neurochemistry international
May 1, 2019
Hidetsugu Fujigaki, Akihiro Mouri, Yasuko Yamamoto et al.
Phencyclidine (PCP) and related NMDA receptor antagonists induce schizophrenia-like symptoms in humans and rodents by blocking neurotransmission at NMDA receptors. The endogenous NMDA receptor antagonist kynurenic acid (KYNA), a product of the tryptophan-kynurenine pathway, is elevated in the prefrontal cortex and cerebrospinal fluid of schizophrenia patients. KYNA elevation affects neurotransmitter release similarly to PCP, suggesting a molecular basis for its role in schizophrenia. This review examines the relationship between PCP and kynurenine pathway metabolites, highlighting how both exogenous and endogenous NMDA receptor antagonists contribute to schizophrenia pathogenesis and discussing dysfunctional glutamatergic signaling as a potential therapeutic target.
The international journal of neuropsychopharmacology
July 1, 2012
Akihiro Mouri, Takenao Koseki, Shiho Narusawa et al.
Different mouse strains show distinct behavioral responses to the psychosis-inducing drug phencyclidine (PCP). C57BL/6N, C57BL/6J, ddY, and ICR mice were compared. PCP caused greater hyperactivity and increased immobility in the forced swim test in ddY mice than in C57BL/6N and C57BL/6J, with ICR mice showing the least effect. However, no strain differences appeared in recognition memory impairment after chronic PCP withdrawal. These findings offer practical guidance for comparing genetic and drug-induced psychosis models in the C57BL/6 strain, which is commonly used in genetic studies, and suggest that strain differences may help identify biological mechanisms underlying PCP-induced behaviors relevant to major mental illnesses.
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.