- P-ISSN1226-9654
- E-ISSN2733-466X
- KCI
사회적 고립과 추적 스트레스를 이용한 복합 스트레스가 청소년기와 성체기 쥐에게 미치는 장기적 효과
Differential effects of Combined Stress during adolescence and adulthood on Anxiety-related Behaviors in Rats
최준식 (고려대학교)
초록
본 연구는 사회적 고립과 추적 스트레스를 이용한 복합 스트레스 모델이 청소년기와 성체기 쥐에게 미치는 장기적 효과를 알아보고자 하였다. 이를 위해 청소년기(생후 5주)와 성체기(생후 8주)의 쥐들은 추적 스트레스 3일 전부터 사회적 고립 처치를 받았으며 각 발달주기 집단은 사회적 고립(social isolation, SI)집단 혹은 사회적 고립과 추적 스트레스(social isolation + chasing stress, SI+C) 집단으로 나뉘었다. 추적 스트레스는 본 연구실에서 새롭게 개발된 스트레스 모델로서, 탈출할 수 없는 원형 트랙에서 빠르게 접근해오는 로봇에게 쫓기는 경험이다. 하루에 20시행씩 총 3일간 SI 집단은 소리자극의 제시를 받았으며 SI+C 집단은 소리자극의 제시와 추적 스트레스를 함께 받았다. 그리고 추적 스트레스 경험으로부터 3주 후에 행동 검사가 실시되었다. 행동 검사로는 추적 스트레스 당시 제시되었던 소리자극에 관한 기억 검사와 불안 관련 행동을 측정하는 높은 십자미로 검사가 진행되었다. 또한 새롭게 경험하는 공포 학습의 양상을 보기 위해 전기 쇼크를 이용한 공포 조건화가 진행되었다. 실험 결과, 추적 스트레스 당시 제시되었던 소리자극에 대한 기억 검사에서 청소년기 SI+C 집단은 성체기 SI+C 집단보다 추적 소리자극 자체에 대해서는 낮은 동결반응을 보였지만 추적 소리자극이 제시되지 않는 시행 간 간격 동안에는 성체기 SI+C 집단과 비슷한 수준의 동결반응을 보였다. 높은 십자미로 검사에서는 청소년기 SI+C 집단이 SI 집단보다 높은 불안 수준을 보였지만 성체기는 두 집단 간 차이가 없었다. 또한 공포 조건화에서 성체기 SI+C 집단은 민감화된 공포 반응을 보인데 반해 청소년기 SI+C 집단은 공포 학습의 결함을 보였다. 이러한 결과는 청소년기에 사회적 고립과 추적 스트레스를 이용한 복합 스트레스를 받을 경우 불안 수준의 증가 뿐 아니라 공포 자극에 대한 적절한 반응을 학습하는 것에 결함이 생긴다는 것을 의미한다. 반면 이러한 복합 스트레스의 효과는 성체기 집단에서는 관찰되지 않았다. 따라서 본 연구는 사회적 고립과 추적 스트레스를 이용한 청소년기 복합 스트레스 모델이 청소년기의 불안 장애에 대한 취약성을 반영하는 동물 모델임을 제안하며 본 모델이 청소년기 불안 장애의 뇌 기전을 밝히는 향후 연구에 활용 가능성이 크다는 점을 시사한다.
- keywords
- Adolescence, Social isolation, Chasing stress, Combined stress, Anxiety, Fear learning, Rat, 청소년기, 사회적 고립, 추적 스트레스, 복합 스트레스, 불안, 공포학습, 쥐
Abstract
We investigated the long-term effects of combined stress using adolescent and adult rats and determined whether there were differential effects depending developmental periods. The combined stress consisted of social isolation and chasing stress. The adolescent (5-weeks old) and adult (8-weeks old) rats were isolated three days prior to chasing stress. Both groups of the rats were assigned to social isolation (SI) or social isolation + chasing stress (SI+C) treatment. Chasing stress is a novel stress paradigm developed by the authors, in which the rats were chased by a fast-approaching robotic construct in an inescapable donut-shaped maze. Three weeks following the chasing stress, the rats were examined for long-term memory of the chasing tone, anxiety-like behavior, and new fear learning. In the chasing tone test, the adolescent SI+C showed a lower level of freezing in response to the chasing tone itself than the adult SI+C. However, there were no differences in freezing levels during inter-trial intervals. In the elevated plus-maze (EPM) test, the adolescent SI+C exhibited increased anxiety-related behaviors, but the adult SI+C did not. In the fear conditioning using footshock, the adult SI+C showed sensitized responses, whereas the adolescent SI+C showed impairment of new fear learning. In sum, the combined stress experienced during adolescence caused long-term disability in reacting properly to a warning cue as well as increased anxiety-related behavior. On the contrary, these effects were not induced by the same treatment during adulthood. Therefore, we propose that combined stress during adolescence, which consisted of social isolation and chasing stress, could be employed as an animal model of anxiety with consideration of the vulnerability of adolescents to anxiety disorders. Further studies are warranted to prove the utility of the new model and the underlying brain mechanism.
- keywords
- Adolescence, Social isolation, Chasing stress, Combined stress, Anxiety, Fear learning, Rat, 청소년기, 사회적 고립, 추적 스트레스, 복합 스트레스, 불안, 공포학습, 쥐
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