Abstract
The aim of this study was to explore effects on anxiety-like behavior of D1 dopamine receptor agonist, SKF-38393, and of D1 dopamine receptor antagonist, SCH-23390, given alone or in combination with a low dose of 17β-estradiol (17β-E2) to ovariectomized (OVX) rats. Two weeks after surgery, OVX rats began 14 days of treatment with the vehicle, a low dose of 17β-E2 (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-E2, or SCH-23390 plus 17β-E2. 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-E2 (5.0 μg/rat, s.c.) resulted in anxiolytic-like effect in OVX rats in the BWM. Repeated treatment with SCH-23390 and 17β-E2 profoundly increased anxiolytic-like effect of single substances exerted per se. Coadministration of SCH-23390 with 17β-E2 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-E2 and SCH-23390 interact to exert anxiolytic-like action and that each of these drugs can potentiate effects of each other.
Highlights
Anxiety is an adaptive response which detects and prepares an individual against a real or a potential threat [1]
The main result of the present study was that SCH-23390 significantly decreased anxiety-related behavior in OVX rats treated with low dose of 17β-E2, suggesting that anxiolyticlike effect of SCH-23390 in the black and white model (BWM) is independent of the presence of 17β-E2
It should be emphasized that combination of SCH-23390 with a low dose of 17β-E2 is more effective for correction of anxiety-like behavior in the OVX rats
Summary
Anxiety is an adaptive response which detects and prepares an individual against a real or a potential threat [1]. Several preclinical and clinical data suggest that DA, acting on D1-like receptors, is one of the most important neuromodulators of fear and anxiety [4]. High numbers of D1 receptors are located within caudate putamen (CPu), nucleus accumbens (NAc), and substantia nigra pars reticulata (SNr) with a less dense distribution in the amygdaloid regions [5]. Evidences suggest that D1 receptors in the CPu, NAc, and SNr facilitate motivated behavior [6, 7], while those in the amygdala are more involved in affective behavior [8, 9]
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