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多巴胺D2激动剂喹那罗啉对雄性和雌性大鼠结节漏斗多巴胺能神经元活动影响的比较。

Comparison of the effects of the dopamine D2 agonist quinelorane on tuberoinfundibular dopaminergic neuronal activity in male and female rats.

作者信息

Eaton M J, Gopalan C, Kim E, Lookingland K J, Moore K E

机构信息

Department of Pharmacology and Toxicology, Michigan State University, East Lansing 48824.

出版信息

Brain Res. 1993 Nov 26;629(1):53-8. doi: 10.1016/0006-8993(93)90480-b.

Abstract

The purpose of the present study was to examine the effects of quinelorane (LY163502), a potent and selective D2 dopaminergic (DA) receptor agonist, on the activity of tuberoinfundibular DA neurons in male and female rats as estimated by determining the concentration of the primary metabolite of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC), in terminals of these neurons in the median eminence (ME). In males, quinelorane produced dose- and time-related increases in the concentration of DOPAC in the Me which was blocked by the D2 receptor antagonist raclopride. The activity of tuberoinfundibular neurons in female rats is higher than it is in males because circulating levels of prolactin tonically stimulate these neurons in the female. In female rats, quinelorane markedly lowered plasma concentrations of prolactin but failed to alter DOPAC concentrations in the ME. Pretreatment of female rats with prolactin antiserum induced hypoprolactinemia and reduced DOPAC concentrations in the ME; in these animals quinelorane increased ME DOPAC concentrations. These results indicate that by acting on D2 receptors quinelorane is able to stimulate tuberoinfundibular DA neurons in both male and female rats, but in female rats the ability of quinelorane to reduce circulating levels of prolactin indirectly reduces the activity of tuberoinfundibular DA neurons and thereby masks the stimulatory action of this drug on these neurons.

摘要

本研究的目的是通过测定正中隆起(ME)中这些神经元终末内多巴胺的主要代谢产物3,4-二羟基苯乙酸(DOPAC)的浓度,来检测强效选择性D2多巴胺能(DA)受体激动剂喹那罗啉(LY163502)对雄性和雌性大鼠结节漏斗部DA神经元活性的影响。在雄性大鼠中,喹那罗啉使ME中DOPAC浓度呈剂量和时间依赖性增加,这一作用被D2受体拮抗剂雷氯必利阻断。雌性大鼠结节漏斗部神经元的活性高于雄性大鼠,因为雌性大鼠中催乳素的循环水平持续刺激这些神经元。在雌性大鼠中,喹那罗啉显著降低血浆催乳素浓度,但未能改变ME中的DOPAC浓度。用催乳素抗血清预处理雌性大鼠可导致低催乳素血症,并降低ME中的DOPAC浓度;在这些动物中,喹那罗啉可增加ME中DOPAC的浓度。这些结果表明,通过作用于D2受体,喹那罗啉能够刺激雄性和雌性大鼠的结节漏斗部DA神经元,但在雌性大鼠中,喹那罗啉降低循环催乳素水平的能力间接降低了结节漏斗部DA神经元的活性,从而掩盖了该药物对这些神经元的刺激作用。

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