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多巴胺在血管紧张素II对长期用乙醇处理的大鼠学习障碍的促进作用中的角色。

The role of dopamine in the facilitatory effect of angiotensin II on impaired learning in rats chronically treated with ethanol.

作者信息

Borawska M H, Kucharewicz G, Wiśniewski K

机构信息

Department of Pharmacology, Medical Academy, Białystok, Poland.

出版信息

Psychopharmacology (Berl). 1988;96(4):500-4. doi: 10.1007/BF02180031.

Abstract

Rats with impaired active avoidance induced by chronic (9 weeks) administration of ethanol were studied. Angiotensin II (ANG II) administered (ICV, 2.0 micrograms) 12 h after the withdrawal of the alcohol not only neutralized the toxic effect of ethanol but also improved learning. When administered on the 5th day after ethanol withdrawal, the effect of ANG II was weaker. Tests of stereotypy and catalepsy were used to study the possible role of the dopaminergic system in this action of ANG II. It was shown that both chronic alcohol treatment and ANG II alone increased apomorphine (1 mg/kg) and amphetamine (7.5 mg/kg) stereotypy but the effects of ANG II were greater. ANG II did not change the stereotypy induced by amphetamine but increased the stereotypy induced by apomorphine in the group of animals chronically treated with alcohol. Haloperidol-induced catalepsy was reduced in these rats. ANG II alone intensified catalepsy and eliminated the effect of ethanol. Both ANG II and alcohol increased striatal dopamine (DA) concentration. This effect of ANG II was significantly greater in the animals chronically treated with alcohol. The above changes were not observed after the DA level had been reduced by alpha-methyl-p-tyrosine (250 mg/kg), nor were changes observed in the striatal DOPAC. The results suggest involvement of the central dopaminergic system in the effect of ANG II on the ethanol-induced impairment of acquisition of active avoidance but, however, the results of the biochemical determinations of DA turnover do not provide an explanation of these changes.

摘要

对通过慢性(9周)给予乙醇诱导主动回避受损的大鼠进行了研究。在撤去酒精12小时后给予血管紧张素II(ANG II,脑室内注射,2.0微克),不仅能抵消乙醇的毒性作用,还能改善学习能力。在撤去乙醇后的第5天给予ANG II,其效果较弱。采用刻板行为和僵住症测试来研究多巴胺能系统在ANG II这一作用中的可能作用。结果表明,慢性酒精处理和单独给予ANG II均增加了阿扑吗啡(1毫克/千克)和苯丙胺(7.5毫克/千克)诱导的刻板行为,但ANG II的作用更强。在慢性酒精处理的动物组中,ANG II没有改变苯丙胺诱导的刻板行为,但增加了阿扑吗啡诱导的刻板行为。这些大鼠中氟哌啶醇诱导的僵住症有所减轻。单独给予ANG II会增强僵住症并消除乙醇的作用。ANG II和酒精均增加了纹状体多巴胺(DA)浓度。在慢性酒精处理的动物中,ANG II的这一作用明显更强。在用α-甲基-对-酪氨酸(250毫克/千克)降低DA水平后,未观察到上述变化,纹状体3,4-二羟基苯乙酸(DOPAC)也未出现变化。结果提示中枢多巴胺能系统参与了ANG II对乙醇诱导的主动回避习得受损的作用,然而,DA周转的生化测定结果并不能解释这些变化。

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