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(+)-UH 232 是 D3 多巴胺受体的部分激动剂,可减弱血管紧张素 IV 和去苯丙氨酸(6)-血管紧张素 IV 在大鼠中的认知作用。

(+)-UH 232, a partial agonist of the D3 dopamine receptors, attenuates cognitive effects of angiotensin IV and des-Phe(6)-angiotensin IV in rats.

机构信息

Department of Clinical Pharmacology, Medical University of Bialystok, Waszyngtona 15A, 15-274 Bialystok, Poland.

出版信息

Eur Neuropsychopharmacol. 2010 Apr;20(4):218-25. doi: 10.1016/j.euroneuro.2009.11.012. Epub 2009 Dec 30.

Abstract

We have recently found that postsynaptic D3 dopamine (DA) receptors appear not to participate in the memory enhancing effects of the angiotensin AT4 receptor agonists angiotensin IV (Ang IV) and des-Phe(6)-Ang IV. In this study we evaluated role of the presynaptic DA D3 receptors in these effects. For that purpose effect of (+)-UH 232, a selective D3 DA receptors partial agonist preferring presynaptic sites, on the pro-cognitive action of intracerebroventricularly (icv) injected Ang IV and des-Phe(6)-Ang IV was examined. Male Wistar rats weighing 180-200 g were used. Both peptides given at the dose of 1 nmol facilitated recall of a passive avoidance (PA) behaviour, improved object recognition (OR), and increased apomorphine-induced stereotype behaviour. In the auxiliary tests performed to control for the unspecific influence of motor (open field, OF) and emotional ('plus' maze, PM) effects of our treatments on the results of the memory tests they had either no (OF) or negligible (PM) effects. Intraperitoneal pre-treatment of the animals with an ineffective on its own dose (1 mg/kg) of (+)-UH 232 abolished or markedly diminished effects of both peptides on PA and OR but did not influence enhancement of stereotypy caused by the peptides.

摘要

我们最近发现,突触后 D3 多巴胺(DA)受体似乎不参与血管紧张素 AT4 受体激动剂血管紧张素 IV(Ang IV)和去苯丙氨酸 6-血管紧张素 IV(des-Phe6-Ang IV)增强记忆的作用。在这项研究中,我们评估了这些作用中前突触 DA D3 受体的作用。为此,我们研究了 (+)-UH 232(一种选择性 D3 DA 受体部分激动剂,优先作用于突触前部位)对侧脑室(icv)注射 Ang IV 和 des-Phe6-Ang IV 的促认知作用。使用体重为 180-200 g 的雄性 Wistar 大鼠。两种肽在 1 nmol 的剂量下均可促进被动回避(PA)行为的回忆,改善物体识别(OR),并增加阿扑吗啡诱导的刻板行为。在进行的辅助测试中,为了控制我们的治疗对记忆测试结果的非特异性运动(开阔场,OF)和情绪(+迷宫,PM)影响,对这些测试进行了控制,结果表明这些影响要么没有(OF),要么可以忽略不计(PM)。动物腹腔内预先用无效剂量(1 mg/kg)的 (+)-UH 232 预处理可消除或显著降低两种肽对 PA 和 OR 的作用,但不影响肽引起的刻板行为的增强。

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