Dhumal V R, Gulati O D, Raghunath P R, Sivaramakrishna N
Br J Pharmacol. 1974 Apr;50(4):513-24. doi: 10.1111/j.1476-5381.1974.tb08584.x.
1 The cerebral ventricles of dogs under intravenous pentobarbitone sodium anaesthesia, were perfused with artificial cerebro-spinal fluid (CSF) at a rate of 0.4-0.5 ml/min from the ventricular to the aqueductal cannulae. The effluent was collected from the aqueductal cannula in 20 min samples. The animals' temperatures were recorded from the rectum.2 gamma-Aminobutyric acid (GABA) 0.1-5 mg when injected into the ventricles produced variable temperature effects. Doses of 0.1 and 0.5 mg always produced hyperthermia and 1 and 5 mg doses sometimes produced hyperthermia and sometimes hypothermia.3 Intraventricular perfusion with 2-bromolysergic acid diethylamide (BOL) and hyoscine did not block hyperthermia. Tests on the rat isolated stomach strip or the guinea-pig isolated superfused ileum for the possible release, respectively, of 5-hydroxytryptamine or acetylcholine by GABA were negative.4 When tested for the presence of prostaglandin E(PGE)-like substances on the isolated rat stomach strip, both the control effluent and the GABA effluent showed activity, the latter being much more potent. There was a temporal correlation between this effect and hyperthermia. Intraventricularly administered sodium salicylate converted the GABA-induced hyperthermia to hypothermia and blocked the release of PGE-like substances.5 Hypothermia induced by GABA alone or in the presence of sodium salicylate was associated with the release of noradrenaline into the effluent.6 Intraventricular administration of GABA in reserpinized dogs produced hyperthermia and not hypothermia. Similar results were obtained with phentolamine perfusion in normal dogs.7 Perfusion with calcium-free solution blocked both the noradrenaline-releasing and hypothermic actions of GABA.8 It is concluded that hyperthermia associated with intraventricular injections of GABA is due to the release of PGE-like substance and hypothermia is due to the release of noradrenaline.
在静脉注射戊巴比妥钠麻醉下的犬，从脑室插管向导水管插管以0.4 - 0.5毫升/分钟的速率灌注人工脑脊液（CSF）。流出液从导水管插管收集，每20分钟取样一次。通过直肠记录动物体温。
向脑室注射0.1 - 5毫克γ-氨基丁酸（GABA）产生不同的体温效应。0.1毫克和0.5毫克剂量总是引起体温升高，1毫克和5毫克剂量有时引起体温升高，有时引起体温降低。
用2-溴麦角酰二乙胺（BOL）和东莨菪碱进行脑室内灌注未阻断体温升高。对大鼠离体胃条或豚鼠离体灌流回肠分别进行试验，以检测GABA是否可能释放5-羟色胺或乙酰胆碱，结果均为阴性。
在离体大鼠胃条上检测前列腺素E（PGE）样物质的存在时，对照流出液和GABA流出液均显示有活性，后者活性更强。这种效应与体温升高之间存在时间相关性。脑室内注射水杨酸钠可将GABA诱导的体温升高转变为体温降低，并阻断PGE样物质的释放。
单独由GABA或在水杨酸钠存在下诱导的体温降低与去甲肾上腺素释放到流出液中有关。
利血平化犬脑室内注射GABA产生体温升高而非体温降低。正常犬酚妥拉明灌注也得到类似结果。
无钙溶液灌注阻断了GABA释放去甲肾上腺素和降低体温的作用。
结论是，脑室内注射GABA相关的体温升高是由于PGE样物质的释放，而体温降低是由于去甲肾上腺素的释放。
