Gnanalingham K K, Robertson R G
Department of Cell and Structural Biology, University of Manchester, UK.
Brain Res. 1994 Mar 21;640(1-2):185-94. doi: 10.1016/0006-8993(94)91872-4.
The effects of chronic 'continuous' infusion and 'intermittent' modes of levodopa/carbidopa administration on apomorphine induced circling behaviour, DA uptake sites (labelled with [3H]mazindol) and D1 and D2 DA receptor binding (labelled with [3H]SCH 23390 and [3H]sulpiride, respectively) were investigated in rats with unilateral 6-OHDA lesions of the medial forebrain bundle. The circling behaviour in response to apomorphine was greatly enhanced following chronic 'intermittent' but not 'continuous' levodopa treatments. Following the 'intermittent' regime, the lower dose of apomorphine induced a period of intense circling with delayed onset and rapid offset, than in rats given either 'continuous' infusion of levodopa or saline. The 6-OHDA lesion itself induced gross depletion of [3H]mazindol binding in all striatal subregions, NAc and OT, but not frontal cortex. [3H]Sulpiride binding in the ventrolateral striatal quadrant was increased on the denervated side and this correlated with the peak contralateral turns in response to 0.5 mg/kg apomorphine challenge. This asymmetry in striatal [3H]sulpiride binding was reduced in both groups of rats receiving levodopa. [3H]sulpiride binding in the NAc and OT and [3H]SCH 23390 binding in the striatum, NAc, OT and SNr were unaffected by DA denervation or either regime of levodopa treatments. 'Continuous' infusion and not 'intermittent' injections of levodopa reduced [3H]mazindol binding in the striatal subregions and the frontal cortex on both the denervated and intact sides. The potentiation of the behavioural response to apomorphine by chronic 'intermittent' levodopa treatment does not correspond with the levodopa induced alterations in striatal or extrastriatal DA receptors. In the same group of animals the narrowing of the duration of response to the lower dose of apomorphine may mimic the fluctuations in response to levodopa, seen clinically in long-term levodopa treated parkinsonian patients.
在单侧内侧前脑束6-羟基多巴胺（6-OHDA）损伤的大鼠中，研究了左旋多巴/卡比多巴的慢性“持续”输注和“间歇”给药模式对阿扑吗啡诱导的转圈行为、多巴胺摄取位点（用[3H]麦角乙脲标记）以及D1和D2多巴胺受体结合（分别用[3H]SCH 23390和[3H]舒必利标记）的影响。慢性“间歇”而非“持续”左旋多巴治疗后，对阿扑吗啡的转圈行为显著增强。在“间歇”给药方案后，较低剂量的阿扑吗啡诱导出一段强烈的转圈期，其起始延迟且结束迅速，这与给予“持续”输注左旋多巴或生理盐水的大鼠不同。6-OHDA损伤本身导致所有纹状体亚区、伏隔核和嗅结节中[3H]麦角乙脲结合显著减少，但额叶皮质未受影响。去神经侧腹外侧纹状体象限中[3H]舒必利结合增加，这与对0.5mg/kg阿扑吗啡激发的对侧峰值转圈相关。接受左旋多巴的两组大鼠纹状体中[3H]舒必利结合的这种不对称性均降低。伏隔核和嗅结节中的[3H]舒必利结合以及纹状体、伏隔核、嗅结节和黑质网状部中的[3H]SCH 23390结合不受多巴胺去神经支配或任何一种左旋多巴治疗方案的影响。左旋多巴的“持续”输注而非“间歇”注射降低了去神经侧和完整侧纹状体亚区及额叶皮质中[3H]麦角乙脲的结合。慢性“间歇”左旋多巴治疗对阿扑吗啡行为反应的增强与左旋多巴诱导的纹状体或纹状体以外多巴胺受体的改变不相符。在同一组动物中，对较低剂量阿扑吗啡反应持续时间的缩短可能模拟了长期接受左旋多巴治疗的帕金森病患者临床上所见的对左旋多巴反应的波动。
