Effects of ovarian hormones on emotional behaviors in dopamine D3 receptor knockout mice.

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.