Anggadiredja Kusnandar, Yamaguchi Taku, Tanaka Hiroyuki, Shoyama Yukihiro, Watanabe Shigenori, Yamamoto Tsuneyuki
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
Brain Res. 2005 Dec 20;1066(1-2):201-5. doi: 10.1016/j.brainres.2005.10.065. Epub 2005 Dec 5.
Cannabinoid withdrawal has been indicated in both human and animal subjects. One of pathways proposed to facilitate cannabinoid action is the arachidonic acid cascade. Previously, we have shown that prostaglandin attenuated the expression of withdrawal signs in tetrahydrocannabinol-dependent mice. It follows that the cascade might participate in the expression of cannabinoid withdrawal. We utilized a quasi abstinence approach (the induction of a state of cannabinoid withdrawal without giving any cannabinoid substances in a naïve animal) to describe the relationship between the change in prostaglandin level, an end product of the arachidonic acid cascade, and the expression of cannabinoid withdrawal. Administration of 10 mg/kg diclofenac, a prostaglandin synthesis inhibitor, i.p. 30 min before SR 141716A induced cannabinoid withdrawal signs in naïve mice, which were comparable to the true abstinence in cannabinoid-tolerant mice. In turn, 10 mg/kg Delta(8)-THC i.p., given 15 min prior to SR 141716A, blocked the expression of these signs. These results suggested that the decrease in prostaglandin level is a prerequisite for the expression of cannabinoid withdrawal.
在人类和动物实验对象中均已证实存在大麻素戒断现象。一种被认为有助于大麻素发挥作用的途径是花生四烯酸级联反应。此前，我们已经表明，前列腺素可减轻四氢大麻酚依赖小鼠的戒断症状表达。由此可见，该级联反应可能参与了大麻素戒断的表达过程。我们采用了一种准戒断方法（在未经接触过大麻素的动物中诱导出大麻素戒断状态，且不给任何大麻素物质）来描述花生四烯酸级联反应的终产物前列腺素水平变化与大麻素戒断表达之间的关系。在SR 141716A诱导未接触过大麻素的小鼠出现大麻素戒断症状前30分钟，腹腔注射10毫克/千克双氯芬酸（一种前列腺素合成抑制剂），所诱导出的戒断症状与大麻素耐受小鼠的真正戒断症状相当。反过来，在SR 141716A前15分钟腹腔注射10毫克/千克Δ⁸-四氢大麻酚，可阻断这些症状的表达。这些结果表明，前列腺素水平降低是大麻素戒断症状表达的一个先决条件。
