Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Center for Translational Medicine, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, People's Republic of China.
Physiol Behav. 2019 Jan 1;198:11-17. doi: 10.1016/j.physbeh.2018.10.003. Epub 2018 Oct 4.
Ovarian hormones reportedly have beneficial effects on affective behaviors. However, the functions of ovarian hormones in neurotransmitter signaling must be identified to understand their role in anxiety and depression. Several studies have provided evidence of the relationship between ovarian hormones and the dopaminergic system, but the interaction between ovarian hormones and dopamine D3 receptor (DRD3) is poorly understood. The aim of the present study was to examine the role of DRD3 in the anxiety-like and depression-like behavioral changes induced by estrogen and progesterone. We subjected D3 receptor knockout (D3KO) and wild-type (WT) mice to a series of behavioral tests. Mice were ovariectomized 4 weeks before testing, and we randomly administered 17β-estradiol (E2, 0.2 mg/kg), progesterone (P4, 10 mg/kg), E2 (0.2 mg/kg) plus P4 (10 mg/kg) or vehicle (VEH, corn oil, 0.2 ml) subcutaneously daily for 9 consecutive days, starting 4 days before the testing day. On the testing day, the mice were injected 30 min prior to behavioral testing. Compared with WT mice in the same treatment group, D3KO mice displayed hyperactivity in the light-dark box test (LDBT) but lower activity in the open field test (OFT). In addition, D3KO mice but not their WT littermates showed behavioral changes after E2 treatment compared with those after VEH treatment in the LDBT only. In depression tests, D3KO-VEH mice displayed significantly longer immobility times than did WT-VEH mice. In addition, only D3KO mice exhibited an obvious decrease in immobility time after E2 and P4 administration. These results indicate that the anxiolytic and antidepressant effects of ovarian hormones can be influenced by DRD3 expression and that DRD3 knockout may induce varying sensitivities to ovarian hormones that depend on various factors, including test paradigms and experiences in animal models. Our research provides a novel insight, i.e., DRD3 may play a role in the efficacy of hormone therapy.
据报道，卵巢激素对情感行为有有益的影响。然而，为了了解其在焦虑和抑郁中的作用，必须确定卵巢激素在神经递质信号传递中的功能。几项研究已经提供了卵巢激素与多巴胺能系统之间关系的证据，但卵巢激素与多巴胺 D3 受体（DRD3）的相互作用知之甚少。本研究旨在研究 DRD3 在雌激素和孕激素诱导的焦虑样和抑郁样行为变化中的作用。我们将 D3 受体敲除（D3KO）和野生型（WT）小鼠进行了一系列行为测试。小鼠在测试前 4 周被卵巢切除术，我们随机给予 17β-雌二醇（E2，0.2mg/kg）、孕酮（P4，10mg/kg）、E2（0.2mg/kg）加 P4（10mg/kg）或载体（VEH，玉米油，0.2ml）皮下注射，连续 9 天，从测试前 4 天开始。在测试当天，在行为测试前 30 分钟注射。与同一治疗组的 WT 小鼠相比，D3KO 小鼠在明暗箱测试（LDBT）中表现出过度活跃，但在旷场测试（OFT）中表现出较低的活动度。此外，仅 D3KO 小鼠在 LDBT 中，而非 WT 同窝小鼠，在 E2 治疗后显示出与 VEH 治疗后的行为变化。在抑郁测试中，D3KO-VEH 小鼠的不动时间明显长于 WT-VEH 小鼠。此外，仅 D3KO 小鼠在给予 E2 和 P4 后表现出明显的不动时间减少。这些结果表明，卵巢激素的抗焦虑和抗抑郁作用可能受到 DRD3 表达的影响，DRD3 敲除可能导致对卵巢激素的敏感性不同，这取决于各种因素，包括动物模型中的测试范式和经验。我们的研究提供了一个新的见解，即 DRD3 可能在激素治疗的疗效中发挥作用。
