CAJ | 학술논문

目的：建立焦虑抑郁共病动物模型，为焦虑抑郁共病的神经生物学机制及治疗方法的研究奠定基础。方法 C57BL／6J小鼠随机分为正常组、模型组和西酞普兰组。采用慢性束缚加孤养方法建模，模型组和西酞普兰组每日束缚4 h（10：00～14：00），连续进行35 d，单笼饲养。造模14 d后，正常组和模型组给予生理盐水，西酞普兰组给予西酞普兰10 mg／kg，腹腔注射，注射剂量为0.1 mL／10 g，给药时间为21 d。应用糖水偏爱实验和强迫游泳实验评价模型抑郁症状的转化效度，应用空场实验和高架十字迷宫实验评价模型焦虑症状的转化效度，同时观察西酞普兰对焦虑抑郁模型行为学改善作用。结果糖水偏爱实验和强迫游泳实验结果显示，慢性束缚模型组糖水偏爱指数明显下降，强迫游泳不动时间明显延长，与正常组比较差异具有显著性（P＜0.01，P＜0.01）。空场实验结果显示，模型组小鼠在中央区停留时间和运动路程明显减少，与正常组比较差异具有显著性（ P＜0.01，P＜0.05）。西酞普兰增加模型小鼠的中央区时间及中央区运动路程（P＜0.05，P＜0.05）。高架十字迷宫实验结果显示，模型组动物进入开臂次数比例及时间比例下降，与正常组比较具有显著性差异（P＜0.05，P＜0.05）。西酞普兰未能逆转这种行为学改变。结论慢性束缚应激模型表现为焦虑抑郁共病，转化效度稳定，可作为焦虑抑郁共病动物模型，用于焦虑抑郁共病生物学机制及其治疗研究。
목적：건립초필억욱공병동물모형，위초필억욱공병적신경생물학궤제급치료방법적연구전정기출。방법 C57BL／6J소서수궤분위정상조、모형조화서태보란조。채용만성속박가고양방법건모，모형조화서태보란조매일속박4 h（10：00～14：00），련속진행35 d，단롱사양。조모14 d후，정상조화모형조급여생리염수，서태보란조급여서태보란10 mg／kg，복강주사，주사제량위0.1 mL／10 g，급약시간위21 d。응용당수편애실험화강박유영실험평개모형억욱증상적전화효도，응용공장실험화고가십자미궁실험평개모형초필증상적전화효도，동시관찰서태보란대초필억욱모형행위학개선작용。결과당수편애실험화강박유영실험결과현시，만성속박모형조당수편애지수명현하강，강박유영불동시간명현연장，여정상조비교차이구유현저성（P＜0.01，P＜0.01）。공장실험결과현시，모형조소서재중앙구정류시간화운동로정명현감소，여정상조비교차이구유현저성（ P＜0.01，P＜0.05）。서태보란증가모형소서적중앙구시간급중앙구운동로정（P＜0.05，P＜0.05）。고가십자미궁실험결과현시，모형조동물진입개비차수비례급시간비례하강，여정상조비교구유현저성차이（P＜0.05，P＜0.05）。서태보란미능역전저충행위학개변。결론만성속박응격모형표현위초필억욱공병，전화효도은정，가작위초필억욱공병동물모형，용우초필억욱공병생물학궤제급기치료연구。
Objective To investigate the effect of chronic restraint stress on the comobidity behavior of anxiety and depression disorders in mice.Method C57BL/6J mice were randomly divided into 3 groups (n=10 per group):control ( normal saline) , chronic restraint stress ( normal saline) , and positive control ( citalopram, 10 mg/kg) .Citalopram and normal saline were administered by intraperitoneal injection.Chronic restraint stress and individual housing was applied to establish the stress model.The mice were individually housed and restrained for 4 h per day in a 50-mL polypropylene conical tube with ventilation holes.This daily restraint was repeated for 35 consecutive days.Sucrose preference test and forced swim test were applied to evaluate the depressive behavior of the mice.Open field test and elevated plus maze test were used to assess the anxiety effect of chronic restraint stress in the mice.Results The sucrose intake was significantly reduced in the chronic restraint stress models compared with the control mice ( P <0.01 ) .The immobility time was increased in the forced swim test (P<0.01).The cumulative duration and distance moved in the center were decreased in the open field test(P<0.01,P<0.05).Chronic treatment with citalopram reversed the above mentioned behavior change. The open arm entry and open arm time were decreased in the elevated plus maze test ( P<0.05,P<0.05) .Citalopram did not reverse this behavior change.Conclusions Mouse models created by chronic restraint and individual housing stress display both anxiety and depressive behavior making them a potent animal model in the treatment of comorbidity of anxiety and depression disorders.