[Development of animal models for schizophrenia based on clinical evidence: expectation for psychiatrists].
Schizophrenic patients show positive symptoms, negative symptoms and cognitive dysfunction. In humans, phencyclidine (PCP), a noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist, reproduces the schizophrenia-like psychosis including positive symptoms, negative symptoms and cognitive dysfunction. Ketamine, another non-competitive NMDA receptor antagonist, also reproduces a schizophrenia-like psychosis in healthy volunteers, and exaggerates the psychosis in schizophrenic patients. It has been hypothesized that insufficient glutamate neurotransmission is involved in the pathophysiology of schizophrenia. Therefore, attempts have been made to develop animal models of schizophrenia by using NMDA receptor antagonists such as PCP, ketamine and dizocilpine. In addition to pharmacological approaches, genetic approaches have been adopted to develop animal models of schizophrenia. The disrupted in schizophrenia 1 (DISC1) gene has been identified as a schizophrenia susceptibility gene based on linkage and single nucleotide polymorphism (SNP) association studies and clinical data, demonstrating that risk SNPs impact on the hippocampal structure and function in clinical and functional roles of DISC1 are analyzed in many kinds of transgenic mice developed. In this review, we focused on PCP and DISC1 transgenic animal models of schizophrenia and summarized recent evidence from several investigators. The basic researchers would need to collaborate with clinical psychiatrists to develop appropriate animal models for schizophrenia based on clinical evidence.
Noda
Yukihiro
Y
Division of Clinical Science and Neuropsychopharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, 150 Yagotoyama, Tenpaku-ku, Nagoya, 468-8503 Japan. y-noda@med.nagoya-u.ac.jp
Mouri
Akihiro
A
Waki
Yukari
Y
Nabeshima
Toshitaka
T
D000818:Animals; D004195:Disease Models, Animal; D019317:Evidence-Based Medicine; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins; D010622:Phencyclidine; D010623:Phencyclidine Abuse; D020641:Polymorphism, Single Nucleotide; D011570:Psychiatry; D012559:Schizophrenia / Q000235:genetics
C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D010622:Phencyclidine