Neurobiology Unit, Wallenberg Neuroscience Center, Department of Experimental Medical Science, Lund University, Lund, Sweden.
Mov Disord. 2010;25 Suppl 1:S174-9. doi: 10.1002/mds.22792.
Recent studies in animal models of Parkinson's disease (PD) have provided evidence that dopamine released from spared serotonin afferents can act as a trigger of dyskinetic movements induced by repetitive, low doses of levodopa. Serotonin neurons have the capacity to store and release dopamine synthesized from systemically administered levodopa. However, because of the lack of any autoregulatory feedback control, dopamine released from serotonin terminals results in excessive swings in extracellular dopamine levels after peripheral administration of levodopa. Such "dysregulated" release of levodopa-derived dopamine is likely to be responsible for the appearance of the abnormal movements in levodopa-primed animals. This mechanism may also play a role in the development of graft-induced dyskinesias in patients that receive fetal neuron transplants, possibly due to the inclusion of serotonin neurons in the grafted ventral midbrain tissue, which contribute to maintain dopamine receptors of the denervated striatum in a supersensitive state.
最近帕金森病（PD）动物模型的研究提供了证据，表明从保留的 5-羟色胺传入纤维释放的多巴胺可以作为重复给予低剂量左旋多巴引起运动障碍的触发因素。5-羟色胺神经元具有储存和释放从全身给予的左旋多巴合成的多巴胺的能力。然而，由于缺乏任何自身调节反馈控制，从 5-羟色胺末梢释放的多巴胺导致外周给予左旋多巴后细胞外多巴胺水平的过度波动。这种“失调”的左旋多巴衍生多巴胺的释放可能是导致给予左旋多巴的动物出现异常运动的原因。该机制也可能在接受胎儿神经元移植的患者中引起移植物诱导的运动障碍的发展中起作用，可能是由于移植的腹侧中脑组织中包含 5-羟色胺神经元，这有助于使去神经纹状体的多巴胺受体保持超敏状态。
