Bruijnzeel Adriaan W, Qi Xiaoli, Guzhva Lidia V, Wall Shannon, Deng Jie V, Gold Mark S, Febo Marcelo, Setlow Barry
Department of Psychiatry, University of Florida, Gainesville, Florida, United States of America.
Department of Neuroscience, University of Florida, Gainesville, Florida, United States of America.
PLoS One. 2016 Apr 11;11(4):e0153327. doi: 10.1371/journal.pone.0153327. eCollection 2016.
Cannabis is the most widely used illicit drug in the world. Delta-9-tetrahydrocannabinol (Δ9-THC) is the main psychoactive component of cannabis and its effects have been well-studied. However, cannabis contains many other cannabinoids that affect brain function. Therefore, these studies investigated the effect of cannabis smoke exposure on locomotor activity, rearing, anxiety-like behavior, and the development of dependence in rats. It was also investigated if cannabis smoke exposure leads to tolerance to the locomotor-suppressant effects of the endogenous cannabinoid anandamide. Cannabis smoke was generated by burning 5.7% Δ9-THC cannabis cigarettes in a smoking machine. The effect of cannabis smoke on the behavior of rats in a small and large open field and an elevated plus maze was evaluated. Cannabis smoke exposure induced a brief increase in locomotor activity followed by a prolonged decrease in locomotor activity and rearing in the 30-min small open field test. The cannabinoid receptor type 1 (CB1) receptor antagonist rimonabant increased locomotor activity and prevented the smoke-induced decrease in rearing. Smoke exposure also increased locomotor activity in the 5-min large open field test and the elevated plus maze test. The smoke exposed rats spent more time in the center zone of the large open field, which is indicative of a decrease in anxiety-like behavior. A high dose of anandamide decreased locomotor activity and rearing in the small open field and this was not prevented by rimonabant or pre-exposure to cannabis smoke. Serum Δ9-THC levels were 225 ng/ml after smoke exposure, which is similar to levels in humans after smoking cannabis. Exposure to cannabis smoke led to dependence as indicated by more rimonabant-precipitated somatic withdrawal signs in the cannabis smoke exposed rats than in the air-control rats. In conclusion, chronic cannabis smoke exposure in rats leads to clinically relevant Δ9-THC levels, dependence, and has a biphasic effect on locomotor activity.
大麻是世界上使用最广泛的非法药物。Δ9-四氢大麻酚（Δ9-THC）是大麻的主要精神活性成分，其作用已得到充分研究。然而，大麻还含有许多其他影响大脑功能的大麻素。因此，这些研究调查了大麻烟雾暴露对大鼠运动活动、竖毛行为、焦虑样行为以及依赖性发展的影响。还研究了大麻烟雾暴露是否会导致对内源性大麻素花生四烯乙醇胺运动抑制作用产生耐受性。通过在吸烟机中燃烧含5.7%Δ9-THC的大麻香烟来产生大麻烟雾。评估了大麻烟雾对大鼠在小和大的旷场以及高架十字迷宫中行为的影响。在30分钟的小旷场试验中，大麻烟雾暴露导致运动活动短暂增加，随后运动活动和竖毛行为长期减少。1型大麻素受体（CB1）拮抗剂利莫那班增加了运动活动，并防止了烟雾引起的竖毛行为减少。烟雾暴露在5分钟的大旷场试验和高架十字迷宫试验中也增加了运动活动。烟雾暴露的大鼠在大旷场中心区域停留的时间更长，这表明焦虑样行为减少。高剂量的花生四烯乙醇胺降低了小旷场中的运动活动和竖毛行为，利莫那班或预先暴露于大麻烟雾并不能阻止这种情况。烟雾暴露后血清Δ9-THC水平为225 ng/ml，这与人类吸食大麻后的水平相似。与空气对照组大鼠相比，大麻烟雾暴露组大鼠出现更多利莫那班诱发的躯体戒断症状，表明暴露于大麻烟雾会导致依赖性。总之，大鼠长期暴露于大麻烟雾会导致具有临床相关性的Δ9-THC水平、依赖性，并对运动活动产生双相效应。
