Effects of SCH-23390 in Combination with a Low Dose of 17β-Estradiol on Anxiety-Like Behavior in Ovariectomized Rats

The aim of this study was to explore effects on anxiety-like behavior of D(1) dopamine receptor agonist, SKF-38393, and of D(1) dopamine receptor antagonist, SCH-23390, given alone or in combination with a low dose of 17β-estradiol (17β-E(2)) to ovariectomized (OVX) rats. Two weeks after surgery, OVX rats began 14 days of treatment with the vehicle, a low dose of 17β-E(2) (5.0 μg/rat, s.c.), SKF-38393 (0.1 mg/kg, i.p.), SCH-23390 (0.1 mg/kg, i.p.), SKF-38393 plus 17β-E(2), or SCH-23390 plus 17β-E(2). The animals were tested in the black and white model (BWM) and the open field test (OFT). SCH-23390 (0.1 mg/kg, i.p.) alone or in a combination with a low dose of 17β-E(2) (5.0 μg/rat, s.c.) resulted in anxiolytic-like effect in OVX rats in the BWM. Repeated treatment with SCH-23390 and 17β-E(2) profoundly increased anxiolytic-like effect of single substances exerted per se. Coadministration of SCH-23390 with 17β-E(2) increased frequency of rearing and grooming in OVX rats in OFT. SKF-38393 (0.1 mg/kg, i.p.) treatment failed to alter anxiety-like behavior in OVX rats in the BWM. The results of the present study suggest that 17β-E(2) and SCH-23390 interact to exert anxiolytic-like action and that each of these drugs can potentiate effects of each other.