Rabin Richard A, Regina Meredith, Doat Mireille, Winter J C
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, 102 Farber Hall, State University of New York at Buffalo, Buffalo, NY 14214-3000, USA.
Pharmacol Biochem Behav. 2002 May;72(1-2):29-37. doi: 10.1016/s0091-3057(01)00720-1.
The role of 5-HT2A-mediated stimulation of phosphoinositide hydrolysis in the discriminative effects of hallucinogens was investigated in PC12 cells stably expressing the rat 5-HT2A receptor (PC12-5-HT2A cells). The hallucinogenic compounds, D-lysergic acid diethylamide (LSD), (-)2,5-dimethoxy-4-methylamphetamine (DOM), psilocybin, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (MDMT) and N,N-diethyltryptamine (DET), all caused a concentration-dependent increase in the generation of [3H]inositol phosphates. The nonhallucinogenic compounds, 6-fluoro-N,N-diethyltryptamine (6-F-DET), lisuride and quipazine, also displayed significant efficacy in stimulating phosphoinositide hydrolysis, while 2-bromo-lysergic acid diethylamide (BOL), which is not a hallucinogen, did not alter inositol phosphate generation. The beta-carbolines, harmaline and harmane, also did not alter phosphoinositide hydrolysis. Comparison of these results with previous drug discrimination studies indicated the apparent lack of correlation between the degree of substitution in LSD- and DOM-trained animals and efficacy in stimulating phosphoinositide hydrolysis. The present study indicates that 5-HT2A-mediated stimulation of phosphoinositide hydrolysis does not appear to be the sole critical signaling mechanism involved in the discriminative effects of hallucinogens.
在稳定表达大鼠5-HT2A受体的PC12细胞（PC12-5-HT2A细胞）中，研究了5-HT2A介导的磷酸肌醇水解刺激在致幻剂辨别效应中的作用。致幻化合物，如D-麦角酸二乙酰胺（LSD）、（-）2,5-二甲氧基-4-甲基苯丙胺（DOM）、裸盖菇素、N,N-二甲基色胺（DMT）、5-甲氧基-N,N-二甲基色胺（MDMT）和N,N-二乙色胺（DET），均引起[3H]肌醇磷酸生成的浓度依赖性增加。非致幻化合物，6-氟-N,N-二乙色胺（6-F-DET）、利苏瑞肽和喹哌嗪，在刺激磷酸肌醇水解方面也显示出显著效果，而不是致幻剂的2-溴麦角酸二乙酰胺（BOL），则不会改变肌醇磷酸的生成。β-咔啉类化合物，骆驼蓬碱和去氢骆驼蓬碱，也不会改变磷酸肌醇水解。将这些结果与先前的药物辨别研究进行比较表明，在LSD和DOM训练的动物中，取代程度与刺激磷酸肌醇水解的效果之间明显缺乏相关性。本研究表明，5-HT2A介导的磷酸肌醇水解刺激似乎不是致幻剂辨别效应中唯一关键的信号传导机制。
