Weiss J M, Cierpial M A, West C H
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Pharmacol Biochem Behav. 1998 Sep;61(1):49-66. doi: 10.1016/s0091-3057(98)00075-6.
Because low motor activity ina swim test has been found to represent "depression-like" behavior in the rat, Sprague-Dawley (SD) albino rats were selectively bred for low motor activity (low struggling time/high floating time) in a swim test, while others were bred for high motor activity (high struggling time/low floating time). Eighty-four male and 42 female SD rats were initially purchased from Charles-River Breeding Laboratories in 1987, their behavior assessed in a 15-min swim test, and selective breeding carried out by mating those male and female rats that showed either low or high levels of motor activity in the test; results from behavioral testing of the first 18 generations produced by this selective breeding process are reported here. Two rat lines have been obtained, Swim Low-Active (SwLo) and Swim High-Active (SwHi) rats, which differ dramatically in swim-test behavior--SwLo rats show little struggling and much floating, while SwHi rats show the reverse. Activity scores of individual SwLo and SwHi rats now show no overlap. Selective breeding has produced bidirectional changes; that is, SwLo rats are considerably less active than randomly bred Sprague-Dawley albino rats, while SwHi rats are considerably more active than randomly bred rats. Measuring activity of SwLo and SwHi rats in other situations--ambulation in the home cage, open-field activity, exploratory activity in a novel, home cage-like situation, and immobility in the Porsolt swim test--revealed that differences are most pronounced when animals respond to acute challenges; under these conditions, SwHi rats show active, assertive behavior, whereas SwLo rats show a distinct absence of this type of response. When SwLo rats from the 8th to the 11th generations were given antidepressant medication [desipramine, (DMI), a tricyclic, or phenelzine, an MAO inhibitor], chronic but not acute administration of both drugs increased swim-test activity of SwLo rats. Buspirone, an anxiolytic, did not increase activity of SwLo rats. Use of animals selectively bred for high and low activity in the swim test may represent a new tool for studying physiological processes relevant to affective disorders and for testing antidepressant drugs/treatments.
由于在游泳测试中低运动活性已被发现代表大鼠的“抑郁样”行为，斯普拉格-道利（SD）白化大鼠在游泳测试中被选择性培育以获得低运动活性（低挣扎时间/高漂浮时间），而其他大鼠则被培育以获得高运动活性（高挣扎时间/低漂浮时间）。1987年，最初从查尔斯-里弗育种实验室购买了84只雄性和42只雌性SD大鼠，在15分钟的游泳测试中评估它们的行为，并通过将在测试中表现出低或高运动活性水平的雄性和雌性大鼠进行交配来进行选择性育种；这里报告了由这种选择性育种过程产生的前18代行为测试结果。已经获得了两个大鼠品系，即游泳低活性（SwLo）大鼠和游泳高活性（SwHi）大鼠，它们在游泳测试行为上有显著差异——SwLo大鼠几乎不挣扎且大量漂浮，而SwHi大鼠则相反。现在单个SwLo和SwHi大鼠的活性评分没有重叠。选择性育种产生了双向变化；也就是说，SwLo大鼠的活性明显低于随机繁殖的斯普拉格-道利白化大鼠，而SwHi大鼠的活性明显高于随机繁殖的大鼠。在其他情况下测量SwLo和SwHi大鼠的活性——在饲养笼中的行走、旷场活动、在类似饲养笼的新环境中的探索活动以及在波索尔特游泳测试中的不动——发现当动物对急性挑战做出反应时差异最为明显；在这些条件下，SwHi大鼠表现出积极、坚定的行为，而SwLo大鼠则明显缺乏这种类型的反应。当给第8至11代的SwLo大鼠服用抗抑郁药物[地昔帕明，（DMI），一种三环类药物，或苯乙肼，一种单胺氧化酶抑制剂]时，两种药物的慢性而非急性给药增加了SwLo大鼠的游泳测试活性。丁螺环酮，一种抗焦虑药，并没有增加SwLo大鼠的活性。使用在游泳测试中为高活性和低活性而选择性培育的动物可能代表了一种研究与情感障碍相关的生理过程以及测试抗抑郁药物/治疗方法的新工具。
