Prenatal exposure to phencyclidine produces abnormal behaviour and NMDA receptor expression in postpubertal mice.
Several studies have shown the disruptive effects of non-competitive N-methyl-d-aspartate (NMDA) receptor antagonists on neurobehavioural development. Based on the neurodevelopment hypothesis of schizophrenia, there is growing interest in animal models treated with NMDA antagonists at developing stages to investigate the pathogenesis of psychological disturbances in humans. Previous studies have reported that perinatal treatment with phencyclidine (PCP) impairs the development of neuronal systems and induces schizophrenia-like behaviour. However, the adverse effects of prenatal exposure to PCP on behaviour and the function of NMDA receptors are not well understood. This study investigated the long-term effects of prenatal exposure to PCP in mice. The prenatal PCP-treated mice showed hypersensitivity to a low dose of PCP in locomotor activity and impairment of recognition memory in the novel object recognition test at age 7 wk. Meanwhile, the prenatal exposure reduced the phosphorylation of NR1, although it increased the expression of NR1 itself. Furthermore, these behavioural changes were attenuated by atypical antipsychotic treatment. Taken together, prenatal exposure to PCP produced long-lasting behavioural deficits, accompanied by the abnormal expression and dysfunction of NMDA receptors in postpubertal mice. It is worth investigating the influences of disrupted NMDA receptors during the prenatal period on behaviour in later life.
Lu
Lingling
L
Department of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, Meijo University, Nagoya, Japan.
Mamiya
Takayoshi
T
Lu
Ping
P
Toriumi
Kazuya
K
Mouri
Akihiro
A
Hiramatsu
Masayuki
M
Kim
Hyoung-Chun
HC
Zou
Li-Bo
LB
Nagai
Taku
T
Nabeshima
Toshitaka
T
D000818:Animals; D001921:Brain / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000633:toxicity*; D005260:Female; D006213:Hallucinogens / Q000633:toxicity*; D006801:Humans; D020547:Lateral Ventricles / Q000187:drug effects; D008297:Male; D001523:Mental Disorders / Q000139:chemically induced* / Q000523:psychology; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000138:chemical synthesis / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D021641:Recognition, Psychology / Q000187:drug effects; D012153:Retention, Psychology / Q000187:drug effects
D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D010622:Phencyclidine