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

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