Anggadiredja Kusnandar, Yamaguchi Taku, Tanaka Hiroyuki, Shoyama Yukihiro, Watanabe Shigenori, Yamamoto Tsuneyuki
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
Brain Res. 2003 Mar 14;966(1):47-53. doi: 10.1016/s0006-8993(02)04169-0.
The present study aimed to clarify the role of the arachidonic acid cascade in mediating the expression of withdrawal signs in cannabinoid-dependent mice. Mice were injected with Delta(8)-tetrahydrocannabinol (THC) at 20 mg/kg (i.p.) every 12 h, 11 times. When SR141716A, a specific cannabinoid CB1 receptor antagonist, at 10 mg/kg (i.p.) was given 4 h after the last THC injection, withdrawal signs such as forepaw licking, facial preening, grooming, forepaw tremor, head shakes and weight loss were clearly observed. PGE(2) at 0.1, 1.0 and 3.2 microg (per animal; i.c.v.) given prior to SR141716A (10 mg/kg, i.p.) dose-dependently decreased the number of forepaw licking, facial preening, grooming and forepaw tremor episodes. Instead of SR141716A, a cyclooxygenase inhibitor diclofenac at 10 mg/kg (i.p.) also precipitated these withdrawal signs. The results suggest that the expression of THC withdrawal is due to a decrease in prostaglandin levels through inactivation of the arachidonic acid cascade in the brain.
本研究旨在阐明花生四烯酸级联反应在介导大麻素依赖小鼠戒断症状表达中的作用。小鼠每12小时腹腔注射20mg/kg的δ⁸-四氢大麻酚（THC），共注射11次。在最后一次注射THC 4小时后，腹腔注射10mg/kg的特异性大麻素CB1受体拮抗剂SR141716A时，可明显观察到戒断症状，如前爪舔舐、面部梳理、理毛、前爪震颤、摇头和体重减轻。在注射SR141716A（10mg/kg，腹腔注射）之前，分别脑室内注射0.1、1.0和3.2μg（每只动物）的前列腺素E₂（PGE₂），可剂量依赖性地减少前爪舔舐、面部梳理、理毛和前爪震颤发作的次数。腹腔注射10mg/kg的环氧化酶抑制剂双氯芬酸，而非SR141716A，也会引发这些戒断症状。结果表明，THC戒断症状的表达是由于大脑中花生四烯酸级联反应失活导致前列腺素水平降低所致。
