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抑郁症慢性轻度应激大鼠模型中的催乳素及其受体

Prolactin and its receptors in the chronic mild stress rat model of depression.

作者信息

Faron-Górecka A, Kuśmider M, Kolasa M, Zurawek D, Gruca P, Papp M, Szafran K, Solich J, Pabian P, Romańska I, Antkiewicz-Michaluk L, Dziedzicka-Wasylewska M

机构信息

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, Kraków 31-343, Poland.

Department of Pharmacology, Institute of Pharmacology, Polish Academy of Sciences, Smętna Street 12, Kraków 31-343, Poland.

出版信息

Brain Res. 2014 Mar 25;1555:48-59. doi: 10.1016/j.brainres.2014.01.031. Epub 2014 Feb 4.

Abstract

Prolactin (PRL) exhibits many physiological functions with wide effects on the central nervous system including stress responses. Our study aimed to investigate the effect of chronic unpredictable mild stress (CMS) - which is a good animal model of depression - on PRL receptor (PRLR) expression in the rat brain. Rats were exposed to CMS for two weeks and subsequently to CMS in combination with imipramine (IMI) treatment for five consecutive weeks. Behavioral deficit measured in anhedonic animals is a reduced intake of sucrose solution. Two weeks of CMS procedure allowed the selection of animals reactive to stress and displaying anhedonia, and the group which is considered as stress-non-reactive as far as behavioral measures are concerned. In this group the elevated level of PRL in plasma was observed, decrease in dopamine release in the hypothalamus, increase in [(125)I]PRL binding to PRLR in the choroid plexus, increase of mRNA encoding the long form of PRLR in the arcuate nucleus and the decrease of mRNA encoding its short form, and decrease in the mRNA encoding dopamine D2 receptor. All these alterations indicate these parameters as involved in the phenomenon of stress-resilience. The prolongation of the CMS procedure for additional five weeks shows the form of habituation to the stressful conditions. The most interesting result, however, was the up-regulation of PRLR in the choroid plexus of rats subjected to full CMS procedure combined with treatment with IMI, which may speak in favor of the role of this receptor in the mechanisms of antidepressant action.

摘要

催乳素(PRL)具有多种生理功能,对包括应激反应在内的中枢神经系统有广泛影响。我们的研究旨在探讨慢性不可预测轻度应激(CMS,一种良好的抑郁症动物模型)对大鼠脑内催乳素受体(PRLR)表达的影响。将大鼠暴露于CMS两周,随后连续五周暴露于CMS并联合丙咪嗪(IMI)治疗。在快感缺失动物中测量的行为缺陷是蔗糖溶液摄入量减少。两周的CMS程序允许选择对应激有反应并表现出快感缺失的动物,以及就行为测量而言被认为对应激无反应的组。在该组中观察到血浆中PRL水平升高、下丘脑多巴胺释放减少、脉络丛中[(125)I]PRL与PRLR的结合增加、弓状核中编码PRLR长形式的mRNA增加以及编码其短形式的mRNA减少,以及编码多巴胺D2受体的mRNA减少。所有这些改变表明这些参数参与了应激恢复现象。将CMS程序延长额外五周显示出对压力条件的适应形式。然而,最有趣的结果是,接受完整CMS程序并联合IMI治疗的大鼠脉络丛中PRLR上调,这可能支持该受体在抗抑郁作用机制中的作用。

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