Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
Increased mortality, hypoactivity, and hypoalgesia in cannabinoid CB1 receptor knockout mice
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DOI：
10.1073/pnas.96.10.5780
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发表时间：
1999-05-11
影响因子：
11.1
通讯作者：
Bonner, TI
中科院分区：
文献类型：
--
作者：
Zimmer, A;Zimmer, AM;Bonner, TI
Delta(9)-四氢大麻酚(Delta(9)-THC)是大麻(大麻)制剂中的主要精神活性成分，可引起中枢神经系统(CNS)反应，包括认知改变和兴奋。这些反应解释了大麻的滥用潜力，而其他作用，如止痛，则表明了潜在的医疗应用。为了研究中枢神经系统中大麻素的主要已知靶标CBI大麻素受体的作用，我们培育了一个CB1基因被破坏的小鼠品系。CB1基因敲除小鼠看起来健康且有生育能力，但它们的死亡率显著增加。在热板和福尔马林试验中，他们也表现出活动减少，环状麻痹增加，以及痛觉减退。Delta(9)-THC诱导的环状癫痫、运动能力低下和体温过低在CBI突变小鼠中完全不存在。相比之下，黑麦在给予Delta(9)-THC后，在甩尾试验和其他行为(舔腹部)和生理(腹泻)反应中仍发现Delta(9)-THC诱导的镇痛作用。因此，Delta(9)-THC的大多数但不是全部的中枢神经系统效应是由CB1受体介导的。
Delta(9)-Tetrahyhrocannabinol (Delta(9)-THC), the major psychoactive ingredient in preparations of Cannabis sativa (marijuana, hashish), elicits central nervous system (CNS) responses, including cognitive alterations and euphoria. These responses account for the abuse potential of cannabis, while other effects such as analgesia suggest potential medicinal applications. To study the role of the major known target of cannabinoids in the CNS, the CBI cannabinoid receptor, we have produced a mouse strain with a disrupted CB1 gene. CB1 knockout mice appeared healthy and fertile, but they had a significantly increased mortality rate. They also displayed reduced locomotor activity, increased ring catalepsy, and hypoalgesia in hotplate and formalin tests. Delta(9)-THC-induced ring-catalepsy, hypomobility, and hypothermia were completely absent in CBI mutant mice. In contrast, rye still found Delta(9)-THC-induced analgesia in the tail-flick test and other behavioral (licking of the abdomen) and physiological (diarrhea) responses after Delta(9)-THC administration. Thus, most, but not all, CNS effects of Delta(9)-THC are mediated by the CB1 receptor.