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对引发撒丁岛嗜酒大鼠5-HT2受体介导行为的药物反应性低。

Low responsiveness to agents evoking 5-HT2 receptor-mediated behaviors in Sardinian alcohol-preferring rats.

作者信息

Ciccocioppo R, Panocka I, Stefanini E, Gessa G L, Massi M

机构信息

Institute of Pharmacology, University of Camerino, Via Scalzino 5, Italy.

出版信息

Pharmacol Biochem Behav. 1995 May;51(1):21-7. doi: 10.1016/0091-3057(94)00322-a.

DOI:10.1016/0091-3057(94)00322-a
PMID:7542392
Abstract

The selective NK3 tachykinin agonist senktide evokes in rodents 5-HT mediated behaviors, including 5-HT2 receptor-mediated wet dog shakes (WDS) and head shakes (HS). It was observed previously that genetically selected Sardinian alcohol-preferring (sP) rats show a small number of WDS and HS following intracerebroventricular (ICV) injection of senktide. The present study was aimed at confirming these observations and at providing information on the reasons accounting for the anomalous response of sP rats. Senktide (500-2000 ng/rat, ICV) produced a much lower number of WDS and HS in sP rats than in nonselected Wistar (nsW) rats. Both behaviors were suppressed by the 5-HT2 antagonist ritanserin (1 mg/kg, subcutaneously), confirming that 5-HT2 receptors mediate the response. HS induced by the ICV injection of 5-HT agonists endowed with marked activity at 5-HT2 receptors, such as quipazine (1500-6000 ng/rat) or DOI (500-3500 ng/rat), were much less pronounced in sP rats than in nsW rats. Moreover, WDS following peripheral injection of 5-hydroxytryptophan, 25-100 mg/kg, and carbidopa, 12.5 mg/kg, were less intense in sP and in ethanol-naive sP rats than in nsW and in Sardinian alcohol-nonpreferring rats. These findings suggest that sP rats have an inherent different regulation of central 5-HT2 mechanisms.

摘要

选择性NK3速激肽激动剂森克肽在啮齿动物中引发5-羟色胺(5-HT)介导的行为,包括5-HT2受体介导的湿狗抖身(WDS)和摇头(HS)。先前观察到,经基因选择的撒丁岛嗜酒(sP)大鼠在脑室内(ICV)注射森克肽后出现少量的WDS和HS。本研究旨在证实这些观察结果,并提供有关sP大鼠异常反应原因的信息。与未选择的Wistar(nsW)大鼠相比,sP大鼠中,ICV注射森克肽(500 - 2000 ng/大鼠)产生的WDS和HS数量要少得多。这两种行为均被5-HT2拮抗剂利坦色林(1 mg/kg,皮下注射)抑制,证实5-HT2受体介导了该反应。ICV注射在5-HT2受体上具有显著活性的5-HT激动剂(如喹哌嗪(1500 - 6000 ng/大鼠)或DOI(500 - 3500 ng/大鼠))所诱导的HS,在sP大鼠中比在nsW大鼠中要轻得多。此外,外周注射25 - 100 mg/kg的5-羟色氨酸和12.5 mg/kg的卡比多巴后,sP大鼠和未接触过乙醇的sP大鼠中的WDS比nsW大鼠和撒丁岛非嗜酒大鼠中的WDS强度更低。这些发现表明,sP大鼠对中枢5-HT2机制具有内在的不同调节。

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