Overstreet D H, Pucilowski O, Rezvani A H, Janowsky D S
Center for Alcohol Studies, University of North Carolina School of Medicine, Chapel Hill 27599-7178, USA.
Psychopharmacology (Berl). 1995 Sep;121(1):27-37. doi: 10.1007/BF02245589.
Flinders Sensitive Line (FSL) rats have been proposed as an animal model of depression because they resemble depressed humans in that they have elevated REM sleep, reduced activity, and increased immobility and anhedonia after exposure to stressors. The present paper reviews experiments on the drug treatment of FSL and control Flinders Resistant Line (FRL) rats related to their utility as an animal model of depression, and presents new information. FSL rats exhibited exaggerated immobility in the forced swim test which is counteracted by the tricyclic antidepressants imipramine and desipramine and the serotonin reuptake blocker sertraline; the low immobility exhibited by the FRL rats is generally unaffected by these compounds. In contrast to these "therapeutic" effects of well recognized antidepressants, lithium and bright light treatment did not alter the exaggerated immobility of FSL rats. Novel data indicated that neither FSL nor FRL rats exhibited alterations in swim test immobility following chronic administration of the psychomotor stimulant amphetamine (2 mg/kg) and the anticholinergic scopolamine (2 mg/kg), which typically reduce immobility after acute administration. However, it was found that the calcium channel blockers verapamil (5 and 15 mg/kg) and nicardipine (10 mg/kg) did reduce the exaggerated immobility in FSL rats following chronic administration, suggesting that these compounds need to be evaluated further in humans. Previous studies have indicated no differences between FSL and FRL rats evaluated in the elevated plus maze, either at baseline or after the administration of diazepam, suggesting that the FSL rat may not differ from controls in anxiety-related behavior. Another recently published study showed that the FSL rat also did not differ from normal Sprague-Dawley rats in startle tests, indicating that the FSL rats do not exhibit behaviors shown in animal models of schizophrenia. These findings confirm the utility of FSL rats as an animal model of depression because the FSL rats do not appear to exhibit behaviors analogous to anxiety or schizophrenia and because they respond "therapeutically" to antidepressants and not psychomotor stimulants.
弗林德斯敏感品系（FSL）大鼠已被提议作为抑郁症的动物模型，因为它们与抑郁症患者相似，在暴露于应激源后，它们的快速眼动睡眠增加、活动减少、不动和快感缺失增加。本文综述了有关FSL大鼠和对照弗林德斯抗性品系（FRL）大鼠作为抑郁症动物模型的药物治疗实验，并提供了新信息。FSL大鼠在强迫游泳试验中表现出过度的不动，三环类抗抑郁药丙咪嗪和地昔帕明以及5-羟色胺再摄取阻滞剂舍曲林可抵消这种现象；FRL大鼠表现出的低不动通常不受这些化合物的影响。与这些公认的抗抑郁药的“治疗”效果相反，锂盐和强光治疗并未改变FSL大鼠过度的不动。新数据表明，慢性给予精神运动兴奋剂苯丙胺（2mg/kg）和抗胆碱能药物东莨菪碱（2mg/kg）后，FSL大鼠和FRL大鼠在游泳试验中的不动均未发生改变，而急性给予这些药物通常会减少不动。然而，发现钙通道阻滞剂维拉帕米（5mg/kg和15mg/kg）和尼卡地平（10mg/kg）在慢性给药后确实减少了FSL大鼠过度的不动，这表明这些化合物需要在人体中进一步评估。先前的研究表明，在高架十字迷宫试验中，无论是基线时还是给予地西泮后，FSL大鼠和FRL大鼠之间均无差异，这表明FSL大鼠在焦虑相关行为方面可能与对照组无差异。另一项最近发表的研究表明，FSL大鼠在惊吓试验中也与正常的斯普拉格-道利大鼠无差异，这表明FSL大鼠未表现出精神分裂症动物模型中出现的行为。这些发现证实了FSL大鼠作为抑郁症动物模型的实用性，因为FSL大鼠似乎未表现出类似于焦虑或精神分裂症的行为，并且因为它们对抗抑郁药而不是精神运动兴奋剂有“治疗”反应。
