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

ABSTRACT

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.