McGregor I S, Arnold J C, Weber M F, Topple A N, Hunt G E
Department of Psychology, University of Sydney, NSW, Australia.
Brain Res. 1998 Aug 17;802(1-2):19-26. doi: 10.1016/s0006-8993(98)00549-6.
Rats were injected with the cannabinoid receptor agonists delta 9-THC (5 mg/kg) or anandamide (20 mg/kg) and assessed for changes in body temperature and locomotor activity. Their brains were then examined for the expression of the immediate early gene c-fos. Similar reductions in body temperature and locomotor activity were seen with delta 9-THC and anandamide although there was evidence, in line with previous reports, to suggest a shorter duration of action of anandamide. delta 9-THC and anandamide caused equally high levels of c-fos expression in the paraventricular nucleus of the hypothalamus and the lateral septum. Both drugs also increased c-fos expression in the central nucleus of the amygdala although the effect was greater with delta 9-THC. Only delta 9-THC caused significant increases in c-fos expression in the nucleus accumbens and caudate-putamen. These differences may be linked to differential activation of cannabinoid receptor subtypes or to differences in efficacy in activating second messenger systems linked to cannabinoid receptors. These findings complement evidence of qualitative differences in the actions of anandamide and delta 9-THC emerging from tests of drug discrimination, cross-tolerance, conditioned place preference and anxiety.
给大鼠注射大麻素受体激动剂δ9-四氢大麻酚(5毫克/千克)或花生四烯乙醇胺(20毫克/千克),并评估其体温和运动活动的变化。然后检查它们的大脑中即早基因c-fos的表达情况。δ9-四氢大麻酚和花生四烯乙醇胺均使体温和运动活动出现类似程度的降低,不过有证据表明,与之前的报道一致,花生四烯乙醇胺的作用持续时间较短。δ9-四氢大麻酚和花生四烯乙醇胺在下丘脑室旁核和外侧隔中引起同样高水平的c-fos表达。两种药物还均增加了杏仁核中央核中的c-fos表达,不过δ9-四氢大麻酚的作用更强。只有δ9-四氢大麻酚使伏隔核和尾状核-壳核中的c-fos表达显著增加。这些差异可能与大麻素受体亚型的不同激活情况有关,或者与激活和大麻素受体相关的第二信使系统的效能差异有关。这些发现补充了从药物辨别、交叉耐受、条件性位置偏爱和焦虑测试中得出的关于花生四烯乙醇胺和δ9-四氢大麻酚作用存在质的差异的证据。