Sprague G L, Craigmill A L
Pharmacol Biochem Behav. 1976 Oct;5(4):409-15. doi: 10.1016/0091-3057(76)90104-0.
The pharmacological interaction between equipotent doses of ethanol (1.35 g/kg) and delta-9-tetrahydrocannabinol (THC, 17 mg/kg) was evaluated in mice using rotarod performance as a measure of drug action. Tolerance ot the effects of ethanol and THC as well as a symmetrical cross-tolerance between these two drugs was demonstrated. Ethanol elimination was not altered by previous treatment with either ethnaol or THC as determined by measuring blood ethanol concentrations with an enzymatic assay. THC metabolite ratios in blood, brain and liver tissues determined after a dose of 3H-THC demonstrated that THC treatment had no effect upon THC metabolism or disposition. Ethanol treatment altered the distribution of THC and also altered hepatic THC metabolism as evidence by the occurrence of increased proportions of polar THC metabolites. No treatment regimens produced lower whole brain levels of subsequent ethanol or THC suggesting that tolerance to ethanol or THC and cross-tolerance between these two drugs does not develop due to lower brain concentrations. A vehicle effect was shown when treatment with a mixture of propylene glycol and Tween-80 altered the metabolic and behavioral effects of subsequently administered THC.
使用转棒试验作为药物作用的衡量指标，在小鼠中评估了等效剂量的乙醇（1.35克/千克）和Δ⁹-四氢大麻酚（THC，17毫克/千克）之间的药理相互作用。研究证实了小鼠对乙醇和THC的耐受性，以及这两种药物之间的对称交叉耐受性。通过酶法测定血乙醇浓度发现，预先给予乙醇或THC均不会改变乙醇的消除过程。给予一剂³H-THC后测定血液、脑和肝组织中的THC代谢物比例，结果表明THC处理对THC的代谢或分布没有影响。乙醇处理改变了THC的分布，并且通过极性THC代谢物比例增加的现象表明乙醇处理改变了肝脏中THC的代谢。没有任何处理方案会使后续乙醇或THC的全脑水平降低，这表明对乙醇或THC的耐受性以及这两种药物之间的交叉耐受性并非由于脑浓度降低所致。当用丙二醇和吐温80的混合物处理改变了随后给予的THC的代谢和行为效应时，显示出一种赋形剂效应。
