Gessa G L, Mascia M S, Casu M A, Carta G
Bernard B. Brodie Department of Neuroscience, University of Cagliari, Italy.
Eur J Pharmacol. 1997 May 26;327(1):R1-2. doi: 10.1016/s0014-2999(97)89683-5.
Two synthetic cannabinoids, WIN 55,212-2 {R-(+)-(2,3-dihydro-5-methyl-3-[{4-morpholinylmethyl]pyrol [1,2,3-de]-1,4-benzoxazin-6-yl)(1-naphthalenyl)methanone monomethanesulfonate} (5.0 and 10 mg/kg i.p.) and CP 55,940 {[1a,2-(R)-5-(1.1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-phenol} {[1a,2-(R)-5-(1,1-dimethylheptyl)-2-[5-hydroxy-2-(3-hydroxypropyl) cyclohexyl]-phenol} (0.5 and 1.0 mg/kg i.p.), inhibited acetylcholine release in the rat hippocampus. The inhibition was prevented by the cannabinoid receptor antagonist, SR 141716A {N-(piperidin-1-yl)-5-(4- chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide} HCl, at the dose of 0.1 mg/kg i.p. Higher doses of SR 141716A (1.0 and 3.0 mg/kg i.p.) themselves increased hippocampal acetylcholine release, suggesting that acetylcholine output is tonically inhibited by endogenous cannabinoids. The results also suggest that the negative effects of marijuana on learning and memory may depend on cannabinoid receptor-mediated inhibition of acetylcholine release.
两种合成大麻素，WIN 55,212-2{R-(+)-(2,3-二氢-5-甲基-3-[{4-吗啉基甲基]吡咯[1,2,3-二]-1,4-苯并恶嗪-6-基)(1-萘基)甲酮甲磺酸盐}(腹腔注射5.0和10毫克/千克)和CP 55,940{[1a,2-(R)-5-(1,1-二甲基庚基)-2-[5-羟基-2-(3-羟丙基)环己基]-苯酚}{[1a,2-(R)-5-(1,1-二甲基庚基)-2-[5-羟基-2-(3-羟丙基)环己基]-苯酚}(腹腔注射0.5和1.0毫克/千克)，抑制大鼠海马体中乙酰胆碱的释放。大麻素受体拮抗剂SR 141716A{N-(哌啶-1-基)-5-(4-氯苯基)-1-(2,4-二氯苯基)-4-甲基-1H-吡唑-3-甲酰胺}盐酸盐以0.1毫克/千克腹腔注射的剂量可预防这种抑制作用。更高剂量的SR 141716A(腹腔注射1.0和3.0毫克/千克)本身会增加海马体中乙酰胆碱的释放，这表明乙酰胆碱的输出受到内源性大麻素的持续抑制。结果还表明，大麻对学习和记忆的负面影响可能取决于大麻素受体介导的对乙酰胆碱释放的抑制作用。
