Fitton A G, Pertwee R G
Br J Pharmacol. 1982 Feb;75(2):409-14. doi: 10.1111/j.1476-5381.1982.tb08802.x.
delta 9-Tetrahydrocannabinol (delta 9-THC) was injected into the preoptic area of the anterior hypothalamus or into the third or fourth cerebral ventricle of the conscious mouse through a chronically implanted cannula and the effects on body temperature and oxygen consumption rate were measured. At an ambient temperature of 22 degrees C, injections of delta 9-THC into the fourth ventricle (5 and 10 microgram) produced dose-dependent falls in rectal temperature. Hypothermia was also observed after injections of the drug into the hypothalamus (5 and 10 microgram) or into the third ventricle (10 microgram). The hypothermia produced by delta 9-THC was associated with a fall in oxygen consumption rate. Falls in rectal temperature and in oxygen consumption rate were significantly greater after injection of delta 9-THC than after injection of the drug vehicle, Tween 80. The falls in rectal temperature and oxygen consumption rate produced by injection of delta 9-THC into the fourth ventricle were abolished by elevation of the ambient temperature from 22 to 32 degrees C. A pretreatment that consisted of subcutaneous injections of delta 9-THC (20 mg/kg) given once daily for three days produced tolerance to the hypothermic effect of the drug when injected on day 4 either into the fourth ventricle (10 microgram) or into a lateral tail vein (2.0 mg/kg). The results suggest that delta 9-THC acts centrally to alter thermoregulation in mice not only when it is injected directly into the hypothalamus or cerebral ventricles but also when it is given intravenously. After intraventricular or intravenous administration the drug may act at extrahypothalamic as well as at hypothalamic sites. The data also support the hypothesis that in mice, tolerance to the hypothermic effect of A9-THC is pharmacodynamic and does not depend on changes in metabolism or distribution of the drug.
将δ9-四氢大麻酚（δ9-THC）通过长期植入的套管注入清醒小鼠下丘脑前部的视前区或第三或第四脑室，并测量其对体温和耗氧率的影响。在22摄氏度的环境温度下，向第四脑室注射δ9-THC（5微克和10微克）会导致直肠温度呈剂量依赖性下降。将该药物注入下丘脑（5微克和10微克）或第三脑室（10微克）后也观察到体温过低。δ9-THC引起的体温过低与耗氧率下降有关。注射δ9-THC后直肠温度和耗氧率的下降明显大于注射药物载体吐温80后。将环境温度从22摄氏度提高到32摄氏度可消除向第四脑室注射δ9-THC所引起的直肠温度和耗氧率下降。一种预处理方法是皮下注射δ9-THC（20毫克/千克），每天一次，连续三天，当在第4天向第四脑室（10微克）或外侧尾静脉（2.0毫克/千克）注射该药物时，会产生对药物体温过低效应的耐受性。结果表明，δ9-THC不仅在直接注入下丘脑或脑室时，而且在静脉注射时，都通过作用于中枢来改变小鼠的体温调节。在脑室内或静脉给药后，该药物可能在下丘脑外以及下丘脑部位起作用。数据还支持这样的假设，即小鼠对δ9-THC体温过低效应的耐受性是药效学的，不依赖于药物代谢或分布的变化。
