흰쥐에서 출생 전 Nitric Oxide Synthase 억제제의 노출이 출생 후 강제 수영 시의 행동 변화에 미치는 영향
Effects of Prenatal Exposure to Nitric Oxide Synthase Inhibitor on Behavioral Changes in Forced Swimming Test in Postnatal Rats
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초록
임신 중 NOS 억제제를 투여 받은 어미 쥐에서 태어난 실험군에서 운동 활성은 저하되고, 강제 수영 시의 부동 상태 시간은 유의하게 길었다. 강제 수영 시의 부동 상태의 연장은 paroxetine에 의해 봉쇄되었다. 이러한 결과들을 통해, 흰쥐에서 출생 전의 NOS 억제제 노출에 의한 출생 후의 운동 활성과 강제 수영 시의 행동 변화가 내인성 우울증의 동물모델이 될 수 있는 가능성을 확인할 수 있었다. 또한, 우울증의 병태생리에 glutamate-NMDA-NO 경로가 관계하며, NO의 작용은 부분적으로 serotonin 신경전달계의 영향을 받는 것으로 추정되었다. 이는 향후 glutamate-NMDA-NO 경로가 우울증 치료의 새로운 길을 열어줄 수 있을 것임을 시사한다.
Abstract
Objectives:It has been demonstrated that nitric oxide (NO) serves as an inter- and intra-cellular messenger in the brain. NO has been implicated in the regulation of monoaminergic neurotransmission and the neuronal growth and synaptogenesis. Recently, NO has been suggested to be involved in the pathogenesis of depression. The aim of this study was to investigate the involvement of NO in the underlying mechanisms of biological vulnerability to depression. Methods:The author measured locomotor activities and postnatal behavioral changes in the forced swimming test (FST) in rats that were exposed prenatally to Nω-nitro-L-arginine, a NO synthase (NOS) inhibitor. It was also investigated that paroxetine, a selective serotonin reuptake inhibitor, may affect the behavioral changes in the FST. Results:Locomotor activities were significantly diminished, and the immobility times in the FST were significantly prolonged in the rats that were exposed prenatally to NOS inhibitor compared with controls. Pretreatment with paroxetine blocked the prolongation of the immobility times in the FST. Conclusion:The results indicate that postnatal behavioral changes due to prenatal exposure to NOS inhibitor in rats may suggest an animal model of endogenous depression, and that the glutamate-NMDA-NO pathway may be involved in the pathophysiology of depression. It is also indicated that the action of NO may, in part, be affected by serotonergic mechanism. This implicates that the glutamate-NMDA-NO pathway may lead to a novel approach to the treatment of depression. (J Korean Neuropsychiatr Assoc 2007;46(5):512-517)
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