흰쥐에서 출생 전의 Nitric Oxide Synthase 억제제의 노출이 출생 후의 MK-801에 의해 유도된 행동 민감성에 미치는 영향

Effects of Prenatal Exposure to Nitric Oxide Synthase Inhibitor on MK-801-Elicited Behavioral Sensitivity in Postnatal Rats

Objectives：The aim of the present study was to investigate the role of prenatal exposure to NOS (nitric oxide synthase) inhibitor during the 3rd trimester of pregnancy on MK-801-elicited behavioral sensitivity in postnatal juvenile rats and the effect of an antipsychotic drug on the change in MK-801-elicited behavioral sensitivity in an attempt to elucidate the participation of NO (nitric oxide) in the pathophysiology of schizophrenia. Methods：L-NA (N-nitro-L-arginine, 25 mg/kg, 40 mg/kg) was injected intraperitoneally in pregnant Sprague-Dawley rats during the 3rd trimester of pregrancy. On postnatal day 35, MK-801-elicited behavioral sensitivity was measured using Neurovision Analysis (automatic motor analysis program). Animals were pretreated with haloperidol or clozapine as a antipsychotic drug before administration of MK-801. Statistical tests of drug effects were performed using ANOVA. A value producing p<0.05 was considered to be significant. Results：MK-801-elicited locomotor activity was significantly increased with prenatal exposure to L-NA in postnatal rats. The change in MK-801-elicited behavioral sensitivity was significantly diminished by pretreatment with haloperidol and clozapine. Conclusion：These findings suggest that NO may in part play an important role in neurodevelopment in that prenatal exposure to NOS inhibitor can influence MK-801-elicited behavioral sensitivity in postnatal rats. These results also indicate that the neurodevelopmental abnormality may predispose schizophrenia