Depression and anxiety are more common among females than males and represent a leading cause of disease-related disability in women. Since the dopamine D1-D2 heteromer is involved in depression- and anxiety-like behavior, the possibility that the receptor complex may have a role in mediating sex differences in such behaviors and related biochemical signaling was explored.In non-human primate caudate nucleus and in rat striatum, females expressed higher density of D1-D2 heteromer complexes and a greater number of D1-D2 expressing neurons compared to males. In rat, the sex difference in D1-D2 expression levels occurred even though D1 receptor expression was lower in female than in male with no difference in D2 receptor expression. In behavioral tests, female rats showed faster latency to depressive-like behavior and a greater susceptibility to the pro-depressive and anxiogenic-like effects of D1-D2 heteromer activation by low doses of SKF 83959, all of which were ameliorated by the selective heteromer disrupting peptide, TAT-D1. The sex difference observed in the anxiety test correlated with differences in low-frequency delta and theta oscillations in the nucleus accumbens. Analysis of signaling pathways revealed that the sex difference in D1-D2 heteromer expression led to differences in basal and heteromer-stimulated activities of two important signaling pathways, BDNF/TrkB and Akt/GSK3/β-catenin.These results suggest that the higher D1-D2 heteromer expression in female may significantly increase predisposition to depressive-like and anxiety-like behavior in female animals.

中文翻译：

---

多巴胺D1-D2受体复合物的表达和信号传导的性别差异会影响抑郁和焦虑样行为。

女性比男性更容易感到抑郁和焦虑，这是女性与疾病相关的残疾的主要原因。由于多巴胺D1-D2异聚体参与抑郁和焦虑样行为，因此探讨了在这种行为和相关生化信号传导中受体复合物可能介导性别差异的可能性。在非人类灵长类尾状核和在大鼠纹状体中，与雄性相比，雌性表达更高的D1-D2异源复合物密度，并表达更多的D1-D2表达神经元。在大鼠中，即使D1受体的表达在雌性中比在男性中低，而在D1-D2的表达水平中也存在性别差异，而D2受体的表达没有差异。在行为测试中 雌性大鼠表现出更快的抑郁样行为潜伏期，并通过低剂量的SKF 83959降低了D1-D2异构体激活前抑郁和焦虑样效应的敏感性，所有这些都通过选择性异源干扰肽TAT得以改善-D1。在焦虑测试中观察到的性别差异与伏隔核中低频δ和θ振荡的差异相关。信号通路的分析表明，D1-D2异源单体表达的性别差异导致BDNF / TrkB和Akt / GSK3 /β-catenin这两个重要信号通路的基础和异源单体刺激活性的差异。 -D2异源单体在雌性动物中的表达可能会显着增加雌性动物对抑郁样和焦虑样行为的易感性。