Levodopa Reverses Cytokine-Induced Reductions in Striatal Dopamine Release
Levodopa Reverses Cytokine-Induced Reductions in Striatal Dopamine Release
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DOI：
10.1093/ijnp/pyu084
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发表时间：
2015-02-01
影响因子：
4.8
通讯作者：
Miller, Andrew H.
中科院分区：
文献类型：
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作者：
Felger, Jennifer C.;Hernandez, Carla R.;Miller, Andrew H.
背景资料：在人类和非人类灵长类动物中使用神经成像和体内微透析的研究表明，炎症细胞因子如干扰素-α减少腹侧纹状体中的多巴胺释放，与抑郁症状包括快感缺乏和精神发育迟缓有关。在此，我们检测了长期用干扰素治疗的恒河猴纹状体多巴胺释放的减少，α可以恢复通过管理的多巴胺前体左旋多巴通过反向体内microdialysis.Results：左旋多巴完全逆转干扰素-α诱导的纹状体多巴胺释放减少。未发现3，4-二羟基苯乙酸与多巴胺的比率发生变化，当未包装的多巴胺通过单胺氧化酶代谢时，该比率会增加。这些发现表明，炎性细胞因子减少多巴胺前体的可用性，而不影响终产物的合成或囊泡包装和/或其代谢。或释放，并为未来的研究提供基础，研究促进多巴胺前体可用于改善炎症增加患者人群的抑郁症状。
Background: Studies using neuroimaging and in vivo microdialysis in humans and nonhuman primates indicate that inflammatory cytokines such as interferon-alpha reduce dopamine release in the ventral striatum in association with depressive symptoms including anhedonia and psychomotor slowing.Methods: Herein, we examined whether reduced striatal dopamine release in rhesus monkeys chronically treated with interferon-alpha can be restored by administration of the dopamine precursor levodopa via reverse in vivo microdialysis.Results: Levodopa completely reversed interferon-alpha-induced reductions in striatal dopamine release. No changes were found in the 3,4-dihydroxyphenylacetic acid to dopamine ratio, which increases when unpackaged dopamine is metabolized via monoamine oxidase.Conclusions: These findings suggest that inflammatory cytokines reduce the availability of dopamine precursors without affecting end-product synthesis or vesicular packaging and/or release and provide the foundation for future studies investigating therapeutic strategies that facilitate availability of dopamine precursors to improve depressive symptoms in patient populations with increased inflammation.