Willis G L, Smith G C, McGrath B P
Brain Res. 1983 May 5;266(2):279-86. doi: 10.1016/0006-8993(83)90659-5.
Intracerebral injections of 6-hydroxydopamine (6-OHDA) which produce deficits in locomotor behaviour and motor performance cause localized accumulation of monoamines as well as depletion of central catecholamines (CA). To determine whether the localized increases in monoamines could be contributing to the behavioural deficits seen after intracerebral 6-OHDA injection, the behavioural and biochemical effects of peripherally administered L-DOPA were compared to those which occurred after central injections of 6-OHDA. Forty-five minutes after the injection of 40 mg/kg of L-DOPA, in animals pretreated with 50 mg/kg of R04-4602, the ability to step down, to retract a limb and to ambulate were significantly impaired. Locomotor behaviour and body temperature of L-DOPA-injected animals were similar to those displayed by animals receiving intracerebral injections of 6-OHDA. Fluorescent histochemical and biochemical assessment of diencephalic and telencephalic CA revealed that depletion of CA was not related to the severity of the motor deficits which occurred, but that increased diencephalic CA were present in impaired animals injected with either 6-OHDA or L-DOPA. These findings support the contention that increased CA in degenerating hypothalamic neurones may contribute to behavioural deficits seen after the injection of 6-OHDA.
脑内注射6-羟基多巴胺(6-OHDA)会导致运动行为和运动能力出现缺陷,引起单胺类物质的局部积累以及中枢儿茶酚胺(CA)的耗竭。为了确定单胺类物质的局部增加是否可能导致脑内注射6-OHDA后出现的行为缺陷,将外周给予左旋多巴(L-DOPA)的行为和生化效应与脑内注射6-OHDA后的效应进行了比较。在注射40mg/kg L-DOPA 45分钟后,对于预先用50mg/kg R04-4602预处理的动物,其下台阶、缩回肢体和行走的能力均受到显著损害。注射L-DOPA的动物的运动行为和体温与接受脑内注射6-OHDA的动物相似。对间脑和端脑CA的荧光组织化学和生化评估显示,CA的耗竭与所出现的运动缺陷的严重程度无关,但在注射6-OHDA或L-DOPA的受损动物中,间脑CA增加。这些发现支持了这样一种观点,即退化的下丘脑神经元中CA的增加可能导致注射6-OHDA后出现的行为缺陷。