Felger Jennifer C, Hernandez Carla R, Miller Andrew H
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA (Drs Felger, Hernandez, and Miller); The Winship Cancer Institute, Emory University, Atlanta, GA (Drs Felger and Miller)
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA (Drs Felger, Hernandez, and Miller); The Winship Cancer Institute, Emory University, Atlanta, GA (Drs Felger and Miller).
Int J Neuropsychopharmacol. 2015 Jan 31;18(4):pyu084. doi: 10.1093/ijnp/pyu084.
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.
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.
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.
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.
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，诸如干扰素-α等炎性细胞因子会降低腹侧纹状体中的多巴胺释放，这与包括快感缺失和精神运动迟缓在内的抑郁症状相关。
在此，我们研究了通过体内反向微透析给予多巴胺前体左旋多巴是否可以恢复长期接受干扰素-α治疗的恒河猴纹状体多巴胺释放的减少。
左旋多巴完全逆转了干扰素-α诱导的纹状体多巴胺释放减少。3,4-二羟基苯乙酸与多巴胺的比率没有变化，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，炎性细胞因子会降低多巴胺前体的可用性，而不会影响终产物合成或囊泡包装和/或释放，并为未来研究促进多巴胺前体可用性以改善炎症增加的患者群体的抑郁症状的治疗策略奠定了基础。
