Escobar Angélica Pilar, Meza Rodrigo C, Gonzalez Marcela, Henny Pablo, Andrés María Estela
Centro de Neurobiología y Fisiopatología Integrativa, Chile.
Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Chile.
IBRO Neurosci Rep. 2022 May 11;12:411-418. doi: 10.1016/j.ibneur.2022.05.002. eCollection 2022 Jun.
The dopamine mesolimbic system is a major circuit involved in controlling goal-directed behaviors. Dopamine D2 receptors (D2R) and kappa opioid receptors (KOR) are abundant Gi protein-coupled receptors in the mesolimbic system. D2R and KOR share several functions in dopamine mesencephalic neurons, such as regulation of dopamine release and uptake, and firing of dopamine neurons. In addition, KOR and D2R modulate each other functioning. This evidence indicates that both receptors functionally interact, however, their colocalization in the mesostriatal system has not been addressed. Immunofluorescent assays were performed in cultured dopamine neurons and adult mice's brain tissue to answer this question. We observed that KOR and D2R are present in similar density in dendrites and soma of cultured dopamine neurons, but in a segregated manner. Interestingly, KOR immunolabelling was observed in the first part of the axon, colocalizing with Ankyrin in 20% of cultured dopamine neurons, indicative that KOR is present in the axon initial segment (AIS) of a group of dopaminergic neurons. In the adult brain, KOR and D2R are also segregated in striatal tissue. While the KOR label is in fiber tracts such as the striatal streaks, corpus callosum, and anterior commissure, D2R is located mainly within the striatum and nucleus accumbens, surrounding fiber tracts. D2R is also localized in some fibers that are mostly different from those positives for KOR. In conclusion, KOR and D2R are present in the soma and dendrites of mesencephalic dopaminergic neurons, but KOR is also found in the AIS of a subpopulation of these neurons.
多巴胺中脑边缘系统是参与控制目标导向行为的主要神经回路。多巴胺D2受体（D2R）和κ阿片受体（KOR）是中脑边缘系统中丰富的Gi蛋白偶联受体。D2R和KOR在多巴胺中脑神经元中具有多种共同功能，如调节多巴胺的释放和摄取以及多巴胺神经元的放电。此外，KOR和D2R相互调节彼此的功能。这些证据表明这两种受体在功能上相互作用，然而，它们在中脑纹状体系统中的共定位尚未得到研究。为了回答这个问题，我们在培养的多巴胺神经元和成年小鼠脑组织中进行了免疫荧光测定。我们观察到，在培养的多巴胺神经元的树突和胞体中，KOR和D2R以相似的密度存在，但呈分离状态。有趣的是，在轴突的起始部分观察到KOR免疫标记，在20%的培养多巴胺神经元中与锚蛋白共定位，这表明KOR存在于一组多巴胺能神经元的轴突起始段（AIS）。在成年大脑中，KOR和D2R在纹状体组织中也呈分离状态。KOR标记位于纤维束中，如纹状体条纹、胼胝体和前连合，而D2R主要位于纹状体和伏隔核内，围绕着纤维束。D2R也定位于一些与KOR阳性纤维大多不同的纤维中。总之，KOR和D2R存在于中脑多巴胺能神经元的胞体和树突中，但在这些神经元的一个亚群的AIS中也发现了KOR。
