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[NAN-190与酮色林联合低剂量17β-雌二醇对产前应激去卵巢大鼠抑郁样行为的联合给药作用特点]

[Pecularities for action of combined administration of NAN-190 and ketanserine with low dose of 17β-estradiol on depression-like behavior in prenatally stressed ovariectomized rats].

作者信息

Fedotova Iu O, Pivina S G, Akulova V K, Ordian N É

出版信息

Ross Fiziol Zh Im I M Sechenova. 2015 Jan;101(1):35-43.

PMID:25868324
Abstract

The aim of the present work was to perform a comparative analysis of 5-HT(1A)- and 5-HT(2A/2C)-receptors blockade effects on depression-like behavior of the adult ovariectomized (OVX) female offspring at estrogen deficiency delivered from their prenatally stressed mothers. The adult prenatally stressed OVX female offspring were chronically (during 14 days) treated by 5-HT(1A)-receptors antagonist--NAN-190 (0.1 mg/kg, s. c.) or 5-HT(2A/2C)-receptors antagonist--ketanserine (0.1 mg/kg, i. p.) alone, or in a combination with its preparartions a low dose of 17β-estradiol (5.0 μg/rat, s. c.). All drugs were administered in 2 weeks after overiectomy during 14 days before and for all period of behavioral testing procedure. The prenatally stressed QVX female offspring were tested in the forced swimming test (FST) and the open field test (OFT). Treatment with NAN-190 alone induced marked depressant-like effect, while NAN-190 administered in a combination with a low dose of 17β-estradiol resulted in an antidepressant-like effect in the FST in the prenatally stressed OVX females as compared to the control prenatally stressed female offspring. Administration ofNAN-190 plus 17β-estradiol led to decreased frequency of rearing, exploratory and grooming behavior in prenatally stressed OVX female offspring in the OFT. Treatment with ketanserine resulted in an antidepressant-like effect in prenatally stressed OVX females in the FST as compared to the control group. However, co-administration of ketanserine with a low dose of 17β-E2 to the prenatally stressed OVX female offspring failed to modify depressant-like behavior in the FST.

摘要

本研究的目的是对5-HT(1A)和5-HT(2A/2C)受体阻断对成年卵巢切除(OVX)雌性后代抑郁样行为的影响进行比较分析,这些后代在雌激素缺乏状态下,其母亲在孕期受到应激。成年期的孕期应激OVX雌性后代被长期(14天)给予5-HT(1A)受体拮抗剂——NAN-190(0.1mg/kg,皮下注射)或5-HT(2A/2C)受体拮抗剂——酮色林(0.1mg/kg,腹腔注射),单独使用或与低剂量的17β-雌二醇(5.0μg/大鼠,皮下注射)联合使用。所有药物在卵巢切除术后2周内给药,持续14天,涵盖行为测试程序的整个前期和测试期。对孕期应激的OVX雌性后代进行强迫游泳试验(FST)和旷场试验(OFT)。单独使用NAN-19治疗可诱导出明显的抑郁样效应,而与低剂量的17β-雌二醇联合使用时,与对照组孕期应激雌性后代相比,NAN-190在孕期应激的OVX雌性大鼠的FST中产生了抗抑郁样效应。给予NAN-190加17β-雌二醇可使孕期应激的OVX雌性后代在OFT中的竖毛、探索和梳理行为频率降低。与对照组相比,使用酮色林治疗可使孕期应激的OVX雌性大鼠在FST中产生抗抑郁样效应。然而,将酮色林与低剂量的17β-E2联合给予孕期应激的OVX雌性后代,未能改变FST中的抑郁样行为。

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