Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA.
Depression of Serotonin Synaptic Transmission by the Dopamine Precursor L-DOPA.
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DOI：
10.1016/j.celrep.2015.07.005
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发表时间：
2015-08-11
期刊：
影响因子：
8.8
通讯作者：
Williams JT
中科院分区：
文献类型：
--
作者：
Gantz SC;Levitt ES;Llamosas N;Neve KA;Williams JT
多巴胺和5-羟色胺（5-HT）神经递质系统之间的失衡与帕金森病（PD）和精神疾病的共病有关。左旋多巴是帕金森病的主要治疗药物，它促进多巴胺的产生和释放。本研究评估了左旋多巴对小鼠脑片单胺突触传递的作用。应用左旋多巴增强D2受体介导的抑制性突触后电流（IPSC）在黑质多巴胺神经元。这种增强主要是由于5-HT末梢释放多巴胺。用L-DOPA处理后，5-HT末端的选择性光遗传学刺激诱发多巴胺释放，产生D2受体介导的IPSC。在中缝背核，L-DOPA对5-HT 1A受体介导的5-HT神经元IPSC产生持久的抑制。当D2受体在中缝背核中表达时，应用L-DOPA导致D2受体介导的IPSC。因此，用L-DOPA治疗引起从5-HT末端的异位多巴胺释放和5-HT介导的突触传递的损失。
Imbalance between the dopamine and serotonin (5-HT) neurotransmitter systems has been implicated in the comorbidity of Parkinson’s disease (PD) and psychiatric disorders. L-DOPA, the leading treatment of PD, facilitates the production and release of dopamine. This study assessed the action of L-DOPA on monoamine synaptic transmission in mouse brain slices. Application of L-DOPA augmented the D2 receptor-mediated inhibitory postsynaptic current (IPSC) in dopamine neurons of the substantia nigra. This augmentation was largely due to dopamine release from 5-HT terminals. Selective optogenetic stimulation of 5-HT terminals evoked dopamine release producing D2 receptor-mediated IPSCs following treatment with L-DOPA. In the dorsal raphe, L-DOPA produced a long-lasting depression of the 5-HT1A receptor-mediated IPSC in 5-HT neurons. When D2 receptors were expressed in the dorsal raphe, application of L-DOPA resulted in a D2 receptor-mediated IPSC. Thus, treatment with L-DOPA caused ectopic dopamine release from 5-HT terminals and a loss of 5-HT-mediated synaptic transmission.