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[5-羟色胺受体1A和2A/2C亚型拮抗剂对去卵巢大鼠抑郁行为及下丘脑c-Fos蛋白表达的影响]

[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].

作者信息

Barabanova S V, Fedotova Iu O, Sapronov N S

出版信息

Eksp Klin Farmakol. 2007 Mar-Apr;70(2):3-7.

PMID:17523441
Abstract

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.

摘要

我们研究了长期单独给予5-羟色胺(5-HT)(2A/2C)受体拮抗剂酮色林(0.1毫克/千克,腹腔注射)和5-HT(1A)受体拮抗剂NAN-190(0.1毫克/千克,腹腔注射),或与17β-雌二醇(每只动物0.5毫克,肌肉注射)联合使用14天,对成年去卵巢(OVX)雌性大鼠抑郁行为以及下丘脑室旁核中c-Fos蛋白表达的影响。大鼠的抑郁通过波索尔特试验进行模拟。采用免疫组织化学技术测定下丘脑室旁核中c-Fos蛋白的表达。在波索尔特试验中,OVX大鼠体内的17β-雌二醇在一定程度上缩短了不动时间。单独使用酮色林可显著缩短OVX大鼠的不动时间。在OVX雌性大鼠中,长期联合给予酮色林和17β-雌二醇可增强酮色林的抗抑郁作用。同时,与完整对照组相比,给予酮色林导致OVX大鼠下丘脑c-Fos蛋白水平显著降低。这些结果表明,卵巢激素系统与参与抑郁机制的血清素能脑系统之间存在实质性相互作用。

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