Tabar J, Hashizume M, Cook C J, Beart P M, Jackson D M
Department of Pharmacology, University of Sydney, New South Wales, Australia.
Pharmacol Biochem Behav. 1989 May;33(1):139-46. doi: 10.1016/0091-3057(89)90443-7.
Mice were treated for 28 days with drinking water containing L-DOPA methyl ester hydrochloride (DME) plus carbidopa, carbidopa alone, or with the vehicle. All mice were then given the vehicle for 1 day and behavioural and biochemical assessments made on the 29th day. On average, mice consumed between 181 and 302 mg/kg of DME (expressed as the base) each day. In behavioural experiments DME- and carbidopa-treated mice were subsensitive to the locomotor stimulating effects of apomorphine, after their pretreatment with reserpine plus alpha-methyl-p-tyrosine to remove endogenous stores of dopamine and to stop its synthesis. Even mice pretreated for only one day with chronic DME or carbidopa displayed some subsensitivity to apomorphine challenge, but the effect was more marked the longer the chronic treatment. Other mice were chronically treated for 28 days with alpha-methylDOPA or vehicle, and these mice when challenged with apomorphine after dopamine depletion (as described above), were also markedly subsensitive to the locomotor activating effects of apomorphine. There were no changes in sensitivity of drug-treated mice to the hypothermic effects of apomorphine, to the stereotypy-inducing effects of apomorphine or d-amphetamine, or to the locomotor activating effects of L-DOPA itself or to bromocriptine. There were, however, some changes in the basal grooming behaviour of both DME- and carbidopa-treated mice, and in their response to SKF38393 challenge. Striatal binding studies with [3H]-spiperone and [3H]-SCH23390 indicated that there were no marked changes in Kd or Bmax of either D-1 or D-2 receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
用含盐酸L-多巴甲酯（DME）加卡比多巴、单独的卡比多巴或赋形剂的饮用水对小鼠进行28天的处理。然后所有小鼠给予赋形剂1天，并在第29天进行行为和生化评估。平均而言，小鼠每天摄入181至302毫克/千克的DME（以碱计）。在行为实验中，在用利血平加α-甲基-对-酪氨酸预处理以去除内源性多巴胺储存并停止其合成后，DME和卡比多巴处理的小鼠对阿扑吗啡的运动刺激作用反应不敏感。即使仅用慢性DME或卡比多巴预处理一天的小鼠对阿扑吗啡激发也表现出一定程度的反应不敏感，但慢性治疗时间越长，这种作用越明显。其他小鼠用α-甲基多巴或赋形剂进行28天的慢性处理，这些小鼠在多巴胺耗竭后（如上所述）用阿扑吗啡激发时，对阿扑吗啡的运动激活作用也明显反应不敏感。药物处理的小鼠对阿扑吗啡的体温过低作用、对阿扑吗啡或d-苯丙胺的刻板行为诱导作用、对L-多巴本身或溴隐亭的运动激活作用的敏感性没有变化。然而，DME和卡比多巴处理的小鼠的基础梳理行为及其对SKF38393激发的反应有一些变化。用[3H]-螺哌隆和[3H]-SCH23390进行的纹状体结合研究表明，D-1或D-2受体的解离常数（Kd）或最大结合容量（Bmax）没有明显变化。（摘要截断于250字）
