Daws L C, Schiller G D, Overstreet D H, Orbach J
School of Biological Sciences, Flinders University of South Australia, Adelaide.
Neuropsychopharmacology. 1991 May;4(3):207-17.
Adult Flinders-Sensitive Line (FSL) rats are significantly more sensitive to the behavioral and physiologic effects of muscarinic agonists than are control, Flinders-Resistant Line (FRL) rats; therefore, they resemble humans with depressive disorders. The present study examined the sensitivity of prepubertal and pubertal FSL and FRL rats to the hypothermic and locomotor inhibitory effects of the muscarinic agonist, oxotremorine, and compared these findings to the regional development of muscarinic receptor binding in similarly aged rats. The FSL rats were significantly more sensitive (-1.85 degrees +/- 0.2 degrees C) than the FRL rats (-0.65 degrees +/- 0.15 degrees C) to the hypothermic effect of 0.25 mumol/kg of oxotremorine at the earliest age tested (18 days postpartum) and became progressively more sensitive throughout the period of testing (FSL -2.8 degrees +/- 0.24 degrees C versus FRL -0.5 degrees +/- 0.16 degrees C at 61 days postpartum, data represent the mean +/- SEM of pooled male and female). Significant increases in muscarinic receptor number in FSL rat brain were observed only in older (61 days postpartum) rats. These results are consistent with the suggestion that the FSL rat is a genetic animal model of depression, but also indicate that the differences in muscarinic sensitivity cannot be accounted for exclusively by differences in the number, per se, of muscarinic receptors.
成年弗林德斯敏感品系（FSL）大鼠对毒蕈碱激动剂的行为和生理效应比对照弗林德斯抗性品系（FRL）大鼠更为敏感；因此，它们类似于患有抑郁症的人类。本研究考察了青春期前和青春期的FSL和FRL大鼠对毒蕈碱激动剂氧化震颤素的体温降低和运动抑制作用的敏感性，并将这些结果与同龄大鼠毒蕈碱受体结合的区域发育情况进行比较。在最早测试的年龄（产后18天），FSL大鼠（-1.85℃±0.2℃）比FRL大鼠（-0.65℃±0.15℃）对0.25μmol/kg氧化震颤素的体温降低作用更为敏感，并且在整个测试期间敏感性逐渐增加（产后61天时，FSL为-2.8℃±0.24℃，而FRL为-0.5℃±0.16℃，数据代表合并的雄性和雌性的平均值±标准误）。仅在较年长（产后61天）的FSL大鼠脑中观察到毒蕈碱受体数量显著增加。这些结果与FSL大鼠是抑郁症的遗传动物模型这一观点一致，但也表明毒蕈碱敏感性的差异不能完全由毒蕈碱受体数量本身的差异来解释。
