Concannon J T, Schechter M D
Pharmacol Biochem Behav. 1982 Jul;17(1):5-9. doi: 10.1016/0091-3057(82)90253-2.
Possible amphetamine-induced changes in locomotor activity were investigated in developing rats administered intracisternal injections of 6-hydroxydopamine (6-OHDA) or its vehicle at 5 days of age. Administration of the dopamine neurotoxin resulted in a significant depletion of whole-brain dopamine to 44% of control levels, whereas norepinephrine levels were not significantly reduced. In normal and 6-OHDA-treated pups activity increased from moderately low levels at 15 days of age to moderately high levels at 25 days of age. However, 6-OHDA-treated rats were hyperactive at 20 days of age. At 25 days, activity in both groups was equal and declined to levels typical for adults. Administration of graded doses of d- and l-amphetamine generally increased activity in both groups of rats, with d-amphetamine being more potent than l-amphetamine. Furthermore, no dose of either amphetamine isomer decreased activity in 6-OHDA-treated, hyperactive rats. Hence, no convincing evidence was found for a "paradoxical calming" effect of amphetamine in hyperactive rats, supporting other recent reports. These results suggest that the neonatal DA-depleted rat does not provide an accurate model system for pre-clinical investigation of the human hyperkinetic syndrome.
在5日龄时经脑池内注射6-羟基多巴胺（6-OHDA）或其溶媒的发育中大鼠中，研究了苯丙胺可能引起的运动活动变化。给予多巴胺神经毒素导致全脑多巴胺显著耗竭至对照水平的44%，而去甲肾上腺素水平未显著降低。在正常和6-OHDA处理的幼崽中，活动从15日龄时的中等低水平增加到25日龄时的中等高水平。然而，6-OHDA处理的大鼠在20日龄时表现为多动。在25日龄时，两组的活动水平相等，并下降到成年大鼠的典型水平。给予不同剂量的d-和l-苯丙胺通常会增加两组大鼠的活动，d-苯丙胺比l-苯丙胺更有效。此外，在6-OHDA处理的多动大鼠中，没有任何剂量的苯丙胺异构体降低活动。因此，没有找到令人信服的证据表明苯丙胺对多动大鼠有“反常平静”作用，这支持了其他近期的报道。这些结果表明，新生期多巴胺耗竭的大鼠不能为人类多动症综合征的临床前研究提供准确的模型系统。
