발달 초기에 모성 분리된 초기 성체 흰쥐의 행동 변화에 있어서 Glutamate성 신경계의 역할

Implication of Glutamatergic Mechanism for the Behavioral Changes Resulting from Early Maternal Separation during the Development in Juvenile Rats

발달 초기에 만성적인 모성 결핍을 경험한 초기 성체 흰쥐에서 나타나는 행동 양상은 우울증에서 관찰되는 행동 양상 과 유사하였다. 모성 결핍을 경험한 실험군이 모성 결핍을 경험하지 않은 대조군에 비해 glutamate성 NMDA 수용체의 비경쟁적 길항제인 MK-801과 NOS 억제제인 L-NA에 더 민감하게 반응하였다는 점에서 발달 초기의 만성적인 모성 결 핍은 glutamate성 NMDA-NO 경로의 정상적인 발달을 저해하는 것으로 추정되었다. 한편, 모성 분리된 실험군에서는 항 우울제에 의해 운동활성은 증가되었고 강제수영시의 부동상태는 단축되었으나 대조군에서는 운동활성과 부동 상태가 항우울제의 영향을 받지 않았다. 결론적으로 저자들은 스트레스에 민감한 glutamate성 NMDA-NO 경로의 취약이 우울 증의 생물학적 소인이 될 수 있다고 제안하는 바이다.

Objective Early maternal separation (EMS) during the development has been known to influence the alteration of behavior in adulthood. Nitric oxide (NO) may have been implicated to play a crucial role in the Meurodevelopment as an intracellular and intercellular messenger. This study was designed to investigate the neurochemical mechanism of the behavioral changes resulting from EMS during the development in juvenile rats. Methods Experimental group consisted of subjects that were removed and weaned from the day on postnatal day 15. Control group were the litters that experienced no EMS until postnatal day 21. On postnatal day 15 and 36, the locomotor activity (LA) was measured. On postnatal day 36 the behavioral changes in the forced swimming test (FST) were also measured. Test drugs were intraperitoneally injected including MK-801 (0.5 mg/kg), Nω-nitro-L-arginine (L-NA, 20 mg/kg), paroxetine (20 mg/kg), and bupropion (150 mg/kg). Results EMS produced the decrease of LA significantly in juvenile rats (p<0.001). Both MK-801 and L-NA increased LA in experimental group (p<0.001) and control group (p<0.05). The degree of increase was higher in experimental group than in control group. However, both paroxetine and bupropion increased LA in experimental group (p<0.001, p<0.05), but not in control group. In the FST, immobility was significantly increased in experimental group compared with control group (p<0.001). The increases of immobility in experimental group were abolished after injecting MK-801, L-NA, paroxetine, and bupropion, respectively. Conclusion These results indicate that EMS during the development can lead to behavioral abnormalities in juvenile rats. The underlying neurochemical mechanism of this behavioral changes may be, in part, related to the glutamatergic NMDA-NO pathway. This suggests that glutamatergic NMDA-NO pathway vulnerable to stress may predispose to depression.