Involvement of D1 receptors in depression-like behavior of ovariectomized rats

The aim of the present study was to explore the mood effects of D1 receptor agonist, SKF-38393 and D1 receptor antagonist, SCH-23390 alone or in combination with a low dose of 17β-estradiol (17β-E2) in the adult ovariectomized female rats (OVX). OVX rats of Wistar strain were used in all experiments. Two weeks after surgery rats were chronically treated with vehicle, a low dose of 17β-E2 (5.0 μg/rat), SKF-38393 (0.1 mg/kg), SCH-23390 (0.1 mg/kg), SKF-38393 plus 17β-E2 or SCH-23390 plus 17β-E2 for 14 days before the forced swimming test. We found that SCH-23390 significantly decreased immobility time in the OVX females. A combination of SCH-23390 with a low dose of 17β-E2 induced more profound decrease of immobility time in the OVX rats compared to the rats treated with SCH-23390 alone. On the contrary, SKF-38393 failed to modify depression-like behavior in the OVX rats. In addition, SKF-38393 significantly blocked the antidepressant-like effect of 17β-E2 in OVX rats. Thus, the D1 receptor antagonist SCH-23390 alone or in combination with a low dose of 17β-E2 exerted antidepressant-like effect in OVX female rats, while the D1 receptor agonist SKF-38393 produced depressant-like profile on OVX rats.