Heffner T G, Seiden L S
J Pharmacol Exp Ther. 1979 Jan;208(1):134-43.
The effects on food intake of repeated administration of d-amphetamine and fenfluramine were examined in rats adapted to a 4 hr/day feeding schedule. Control rats given daily injections of amphetamine before food access rapidly developed a partial tolerance to the food intake reducing effect of amphetamine. However, rats given a 6-hydroxydopamine (6-HDA) treatment which produced a large selective depletion of dopamine in brain failed to display tolerance to amphetamine-induced anorexia after either 10 or 23 days of amphetamine injections. Although higher than normal doses of amphetamine were required to reduce feeding in 6-HDA-treated rats, control rats displayed tolerance after repeated injections of drug doses which were either equianorexic or equivalent to doses used in rats given 6-HDA. Furthermore, 6-HDA-treated rats failed to display tolerance to the low amphetamine doses normally used in control rats. In contrast to the results with amphetamine, both control and 6-HDA-treated rats displayed tolerance to the anorexic effect of fenfluramine. These results suggest that central dopaminergic neurons are involved in the tolerance which normally develops to the anorexic effect of amphetamine.
在适应每天4小时进食时间表的大鼠中，研究了重复给予d-苯丙胺和芬氟拉明对食物摄入量的影响。在进食前每日注射苯丙胺的对照大鼠迅速对苯丙胺减少食物摄入的作用产生了部分耐受性。然而，接受6-羟基多巴胺（6-HDA）处理致使大脑中多巴胺大量选择性耗竭的大鼠，在注射苯丙胺10天或23天后，并未对苯丙胺诱发的厌食表现出耐受性。尽管在6-HDA处理的大鼠中需要高于正常剂量的苯丙胺来减少进食，但对照大鼠在重复注射等效厌食剂量或与给予6-HDA的大鼠所用剂量相当的药物后表现出了耐受性。此外，6-HDA处理的大鼠对对照大鼠通常使用的低剂量苯丙胺未表现出耐受性。与苯丙胺的结果相反，对照大鼠和6-HDA处理的大鼠对芬氟拉明的厌食作用均表现出耐受性。这些结果表明，中枢多巴胺能神经元参与了通常对苯丙胺厌食作用产生的耐受性。
