Antidepressant drugs are recommended for the treatment of Parkinson's disease (PD)-associated depression but their role in the modulation of L-DOPA-induced behavioral and neurochemical markers is poorly explored. The aim of the present study was to examine the impact of the tricyclic antidepressant amitriptyline and L-DOPA, administered chronically alone or in combination, on rotational behavior, monoamine levels and binding of radioligands to their transporters in the dopaminergic brain structures of unilaterally 6-OHDA-lesioned rats. Binding of [³H]nisoxetine to noradrenaline transporter (NET), [³H]GBR 12,935 to dopamine transporter (DAT) and [³H]citalopram to serotonin transporter (SERT) were analyzed by autoradiography. Amitriptyline administered alone did not induce rotational behavior but in combination with L-DOPA increased the number of contralateral rotations much more strongly than L-DOPA alone. The combined treatment also significantly increased the tissue dopamine (DA) content in the ipsilateral striatum and substantia nigra (SN) vs. L-DOPA alone. 6-OHDA-mediated lesion of nigrostriatal DA neurons drastically reduced DAT and NET bindings in the ipsilateral striatum. In the ipsilateral SN, DAT binding decreased while NET binding rose. SERT binding increased significantly mainly in the SN. Amitriptyline administered alone or jointly with L-DOPA had no effect on DAT binding on the lesioned side, significantly decreased SERT binding in the striatum and SN while NET binding only in the SN. Since in the DA-denervated striatum, SERT is mainly responsible for reuptake of L-DOPA-derived DA while in the SN, SERT and NET are involved, the inhibition of these transporters by antidepressant drugs may improve dopaminergic transmission and consequently motor behavior.

建议将抗抑郁药用于治疗帕金森氏病（PD）相关的抑郁症，但在调节L-DOPA诱导的行为和神经化学标志物方面的作用却很少。本研究的目的是研究长期单独或联合给药的三环抗抑郁药阿米替林和L-DOPA对单侧多巴胺能脑结构中多巴胺能脑结构的旋转行为，单胺水平和放射性配体与其转运蛋白的结合的影响。 OHDA损伤的大鼠。[ ³ H]尼西汀与去甲肾上腺素转运蛋白（NET），[ ³ H] GBR 12,935与多巴胺转运蛋白（DAT）和[ ³通过放射自显影分析H]西酞普兰至5-羟色胺转运蛋白（SERT）。单独使用阿米替林不会引起旋转行为，但是与单独使用L-DOPA联合使用时，与L-DOPA联合使用时，对侧旋转次数的增加要大得多。与单独使用L-DOPA相比，联合治疗还显着增加了同侧纹状体和黑质（SN）中的组织多巴胺（DA）含量。6-OHDA介导的黑纹状体DA神经元病变大大减少了同侧纹状体中的DAT和NET结合。在同侧SN中，DAT结合减少，而NET结合增加。SERT绑定主要在SN中显着增加。单独或与L-DOPA联合给药的阿米替林对病变侧的DAT结合没有影响，显着减少了纹状体和SN中的SERT结合，而NET结合仅在SN中。由于在DA去神经纹状体中，SERT主要负责L-DOPA衍生的DA的再摄取，而在SN，SERT和NET中则涉及，因此抗抑郁药对这些转运蛋白的抑制作用可能会改善多巴胺能传递，从而改善运动行为。