Myers R D, Ruwe W D
Pharmacol Biochem Behav. 1982 Feb;16(2):321-7. doi: 10.1016/0091-3057(82)90167-8.
In adult male Sprague-Dawley rats, stainless steel guide cannulae were implanted stereotaxically in either the lateral or third cerebral ventricle. Postoperatively, each animal was maintained at an ambient temperature of 22 degrees C. Just prior to the intragastric gavage of 4.0 g/kg ethyl alcohol (20% solution) individual animals were fitted with a colonic thermistor probe. Then, control CSF, a monoaminergic receptor antagonist, or a Ca++ ion chelating agent, EGTA, was infused into either the lateral or third ventricle (ICV) in a volume of 10.0 microliter. Phentolamine (20.0 micrograms), butaclamol (10.0 micrograms), or methysergide (20.0 micrograms) injected ICV all failed to prevent the thermolytic action of alcohol. The fall of 1.5 to 2.0 degrees C in the rat's colonic temperature, ordinarily caused by alcohol, was the same as that without the antagonists and lasted 3.0 to 4.0 hrs. EGTA infused into the rat's lateral cerebral ventricle also did not interfere with alcohol's poikilothermic action. However, EGTA infused into the third cerebral ventricle completely blocked alcohol's effect in lowering the body temperature of the rat. These results suggest that: (1) alcohol's profound effects on body temperature are not mediated by 5-HT, norepinephrine or dopamine pathways which are thought to underlie the mechanisms in the hypothalamus for thermoregulation; and (2) the temperature set-point mechanism, controlled by the ratio of diencephalic Na+ to Ca++ ions, is incapacitated by alcohol. Restoration of the ratio in the diencephalon by the direct, local chelation of Ca++ ions that eliminates alcohol's deleterious effects on body temperature.
在成年雄性Sprague-Dawley大鼠中,将不锈钢引导套管立体定向植入侧脑室或第三脑室。术后,每只动物维持在22摄氏度的环境温度下。就在以4.0 g/kg乙醇(20%溶液)进行胃内灌胃之前,给每只动物安装一个结肠热敏电阻探头。然后,将对照脑脊液、单胺能受体拮抗剂或Ca++离子螯合剂乙二醇双四乙酸(EGTA)以10.0微升的体积注入侧脑室或第三脑室(脑室内)。脑室内注射酚妥拉明(20.0微克)、布他拉莫(10.0微克)或麦角新碱(20.0微克)均未能阻止酒精的解热作用。通常由酒精引起的大鼠结肠温度下降1.5至2.0摄氏度,与未使用拮抗剂时相同,持续3.0至4.0小时。注入大鼠侧脑室的EGTA也不干扰酒精的变温作用。然而,注入第三脑室的EGTA完全阻断了酒精降低大鼠体温的作用。这些结果表明:(1)酒精对体温的深远影响不是由5-羟色胺、去甲肾上腺素或多巴胺途径介导的,这些途径被认为是下丘脑体温调节机制的基础;(2)由间脑Na+与Ca++离子比例控制的体温调定点机制因酒精而失效。通过直接局部螯合Ca++离子恢复间脑中的比例,从而消除酒精对体温的有害影响。