CHANGES IN BODY-TEMPERATURE AND OXYGEN-CONSUMPTION RATE OF CONSCIOUS MICE PRODUCED BY INTRAHYPOTHALAMIC AND INTRACEREBROVENTRICULAR INJECTIONS OF DELTA-9-TETRAHYDROCANNABINOL
CHANGES IN BODY-TEMPERATURE AND OXYGEN-CONSUMPTION RATE OF CONSCIOUS MICE PRODUCED BY INTRAHYPOTHALAMIC AND INTRACEREBROVENTRICULAR INJECTIONS OF DELTA-9-TETRAHYDROCANNABINOL
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DOI：
10.1111/j.1476-5381.1982.tb08802.x
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发表时间：
1982-01-01
影响因子：
7.3
通讯作者：
PERTWEE, RG
中科院分区：
文献类型：
--
作者：
FITTON, AG;PERTWEE, RG
1将Δ9-四氢大麻酚（Δ9-THC）通过长期植入的套管注射到清醒小鼠的下丘脑前部的视前区或第三或第四脑室中，并测量对体温和耗氧率的影响。2在22°C的环境温度下，将Δ9-THC（5和10 μg）注射到第四脑室中产生直肠温度的剂量依赖性福尔斯下降。将药物注射到下丘脑（5和10 μg）或第三脑室（10 μg）后也观察到体温降低。3 Δ9-THC产生的体温降低与耗氧率下降相关。注射Δ9-THC后直肠温度和耗氧率的福尔斯下降显著大于注射药物载体后，吐温80.4通过将Δ 9-THC注射到第四脑室中产生的直肠温度和氧消耗率的福尔斯下降通过将环境温度从22 ° C升高到32° C而消除。当在第4天注射到第四脑室（10 μg）或侧尾静脉时，每天一次给予20 mg/kg（持续3天）产生了对药物低温效应的耐受性（2.0毫克/千克）.6结果表明，Δ9-THC不仅在直接注射到下丘脑或脑室时，而且在给予静脉注射脑室内或静脉内给药后，药物可作用于下丘脑外和下丘脑部位。数据还支持以下假设：在小鼠中，对Δ9-THC的低温效应的耐受性是药效学的，并且不依赖于药物代谢或分布的变化。
1Δ9‐Tetrahydrocannabinol (Δ9‐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.2At an ambient temperature of 22°C, injections of Δ9‐THC into the fourth ventricle (5 and 10 μg) produced dose‐dependent falls in rectal temperature. Hypothermia was also observed after injections of the drug into the hypothalamus (5 and 10 μg) or into the third ventricle (10 μg).3The hypothermia produced by Δ9‐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 Δ9‐THC than after injection of the drug vehicle, Tween 80.4The falls in rectal temperature and oxygen consumption rate produced by injection of Δ9‐THC into the fourth ventricle were abolished by elevation of the ambient temperature from 22 to 32°C.5A pretreatment that consisted of subcutaneous injections of Δ9‐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 μg) or into a lateral tail vein (2.0 mg/kg).6The results suggest that Δ9‐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 Δ9‐THC is pharmacodynamic and does not depend on changes in metabolism or distribution of the drug.