Dopamine (DA) is involved in stress and stress-related illnesses, including many psychiatric disorders. Corticotropin-releasing factor (CRF) plays a role in stress responses and targets the ventral midbrain DA system, which is composed of DA and non-DA cells, and divided into specific subregions. Although CRF inputs to the midline A10 nuclei (“classic VTA”) are known, in monkeys, CRF-containing terminals are also highly enriched in the expanded A10 parabrachial pigmented nucleus (PBP) and in the A8 retrorubral field subregions. We characterized CRF-labeled synaptic terminals on DA (tyrosine hydroxylase, TH+) and non-DA (TH–) cell types in the PBP and A8 regions using immunoreactive electron microscopy (EM) in male and female macaques. CRF labeling was present mostly in axon terminals, which mainly contacted TH-negative dendrites in both subregions. Most CRF-positive terminals had symmetric profiles. In both PBP and A8, CRF symmetric (putative inhibitory) synapses onto TH-negative dendrites were significantly greater than asymmetric (putative excitatory) profiles. This overall pattern was similar in males and females, despite shifts in the size of these effects between regions depending on sex. Because stress and gonadal hormone shifts can influence CRF expression, we also did hormonal assays over a 6-month time period and found little variability in basal cortisol across similarly housed animals at the same age. Together our findings suggest that at baseline, CRF-positive synaptic terminals in the primate PBP and A8 are poised to regulate DA indirectly through synaptic contacts onto non-DA neurons.

中文翻译：

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雄性和雌性猕猴中促肾上腺皮质激素释放因子-多巴胺的相互作用：超越经典的 VTA

多巴胺 (DA) 与压力和压力相关疾病有关，包括许多精神疾病。促肾上腺皮质激素释放因子 (CRF) 在应激反应中发挥作用，并针对腹侧中脑 DA 系统，该系统由 DA 和非 DA 细胞组成，并分为特定的子区域。尽管 CRF 输入到中线 A10 核（“经典 VTA”）是已知的，但在猴子中，包含 CRF 的末端在扩展的 A10 臂旁色素核 (PBP) 和 A8 红核后区亚区域也高度富集。我们使用免疫反应电子显微镜（EM）对雄性和雌性猕猴的 PBP 和 A8 区域的 DA（酪氨酸羟化酶，TH+）和非 DA（TH–）细胞类型上 CRF 标记的突触末端进行了表征。 CRF 标记主要存在于轴突末端，其主要接触两个分区中的 TH 阴性树突。大多数 CRF 阳性端子具有对称轮廓。在 PBP 和 A8 中，TH 阴性树突上的 CRF 对称（假定的抑制性）突触明显大于不对称（假定的兴奋性）突触。尽管这些影响的大小因性别而异，但男性和女性的总体模式相似。由于压力和性腺激素的变化会影响 CRF 的表达，因此我们还进行了 6 个月的激素测定，发现相同年龄的相似饲养动物的基础皮质醇几乎没有变化。我们的研究结果表明，在基线时，灵长类 PBP 和 A8 中的 CRF 阳性突触末梢准备通过与非 DA 神经元的突触接触来间接调节 DA。