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脑室内注射百日咳毒素治疗与乙醇的共济失调和体温过低效应之间的相互作用。

Interactions of intracerebroventricular pertussis toxin treatment with the ataxic and hypothermic effects of ethanol.

作者信息

Durcan M J, Lister R G, Morgan P F, Linnoila M

机构信息

Laboratory of Clinical Studies, National Institute on Alcohol Abuse & Alcoholism, DICBR, Bethesda, MD 20892.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 1991 Aug;344(2):252-8. doi: 10.1007/BF00167227.

Abstract

Pretreatment with pertussis toxin (0.5 and 1.0 microgram/animal, i.c.v., seven days prior to testing) reversed the reduction in locomotor activity in the holeboard test caused by administration of the alpha 2-adrenoceptor agonist, medetomidine (0.1 mg/kg, i.p.). Intrinsic behavioral effects of pertussis toxin treatment were also observed, these included a reduction in exploratory head-dipping and an increase in locomotor activity. These doses of pertussis toxin also reduced the ataxia induced by a 2.4 g/kg dose of ethanol. Pertussis toxin treated animals also exhibited a diminished hypothermic response to ethanol (2 g/kg), although the pertussis toxin treated animals had lower body temperatures prior to ethanol administration compared to sham treated animals. Neither the behavioral effect of pertussis holotoxin in the holeboard nor its effects on reversing medetomidine hypolocomotion or ethanol-induced ataxia were seen following administration of the binding oligomer of pertussis toxin which binds to the cell membrane but does not possess the enzymatically active subunit. These findings implicate mechanisms involving pertussis toxin sensitive G-proteins in modulating some behavioral and physiological effects of ethanol.

摘要

用百日咳毒素预处理(0.5和1.0微克/动物,脑室内注射,在测试前七天)可逆转因给予α2 - 肾上腺素能受体激动剂美托咪定(0.1毫克/千克,腹腔注射)而导致的旷场试验中运动活动的减少。还观察到了百日咳毒素处理的内在行为效应,这些效应包括探索性头部下垂减少和运动活动增加。这些剂量的百日咳毒素还减轻了2.4克/千克剂量乙醇诱导的共济失调。百日咳毒素处理的动物对乙醇(2克/千克)的体温过低反应也减弱,尽管与假处理动物相比,百日咳毒素处理的动物在给予乙醇前体温较低。在给予与细胞膜结合但不具有酶活性亚基的百日咳毒素结合寡聚物后,未观察到百日咳全毒素在旷场试验中的行为效应,也未观察到其对逆转美托咪定低运动活性或乙醇诱导的共济失调的影响。这些发现表明,涉及百日咳毒素敏感G蛋白的机制在调节乙醇的某些行为和生理效应中起作用。

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