Effects of antagonists of 1A and 2A/2C subtypes of serotonin receptors on the depressive behavior and expression of c-Fos protein in hypothalamus of ovariectomized rats

摘要

We have studied the influence of a chronic administration of the 5-HT(2A/2C) receptor antagonist ketanserin (0.1 mg/kg, i.p.) and the 5-HT(1A) receptor antagonist NAN-190 (0.1 mg/kg, i.p.) alone or in combinations with 17beta-estradiol (0.5 mg per animal, i.m.) for 14 days on the depressive behavior and expression of c-Fos protein in the paraventricular nucleus of hypothalamus in adult ovariectomized (OVX) female rats. The depression in rats was modeled by the Porsolt test. The c-Fos protein expression in the paraventricular nucleus of hypothalamus was determined using immunohistochemical techniques. In the Porsolt test, 17beta-estradiol in OVX rats reduced the immobilization time to some extent. Ketanserin alone significantly decreased the immobilization time in OVX rats. The chronic administration of ketanserin in combination with 17beta-estradiol in OVX females potentiated the antidepressant effect of ketanserin. At the same time, ketanserin administration led to a significant decrease in the level of c-Fos protein in the hypothalamus in OVX rats as compared to the intact control. These results are indicative of a substantial interaction between the ovarian hormonal system and the serotoninergic brain system involved the mechanisms of depression.