Ahn H S, Makman M H
Brain Res. 1979 Feb 16;162(1):77-88. doi: 10.1016/0006-8993(79)90757-1.
The influence of D-lysergic acid diethylamide (LSD) and mescaline on adenylate cyclase activity was studied in homogenates of Cebus and rhesus monkey anterior limbic cortex (ALC), frontal cortex (FC), caudate nucleus and retina. Previous studies have shown these tissues to contain dopamine-stimulated adenylate cyclase (AC). In addition, we are now reporting the presence of a dopamine-sensitive adenylate cyclase in the auditory cortex. AC of ALC and auditory cortex was stimulated by LSD and mescaline, whereas activity of FC, caudate nucleus and retina was not stimulated by the same agents. In contrast to regional specificity for stimulation, LSD was capable of antagonizing dopamine-stimulated activity in all brain regions examined. LSD and mescaline produced similar maximal stimulation (about 70%) of AC of ALC homogenates, but the EC50 for LSD (0.43 micrometer) was about one-tenth that for mescaline (4.5 micrometer). Similar relative potencies were also observed for the auditory cortex enzyme. Although much weaker than LSD, methamphetamine also produced a dose-dependent stimulation of ALC AC. Both agonist and antagonist effects of the hallucinogens appear to involve interaction with dopamine receptors; LSD- or methamphetamine-stimulated activity in ALC was blocked by haloperidol and fluphenazine, which are dopamine antagonists, but not by phentolamine, an alpha-receptor blocker. Antagonism of dopamine by LSD in both ALC and FC was found to be competitive and mescaline was an effective but weaker antagonist than was LSD. In addition, neither histamine--nor Gpp(NH)p--stimulated activity of FC was inhibited by LSD. It is proposed that the occurrence of dopamine agonistic action of hallucinogens in only certain regions of primate brain may provide a basis for at least some of the behavioral effects of LSD, mescaline and methamphetamine in primates.
研究了D-麦角酸二乙酰胺（LSD）和三甲氧苯乙胺对卷尾猴和恒河猴的前边缘叶皮质（ALC）、额叶皮质（FC）、尾状核及视网膜匀浆中腺苷酸环化酶活性的影响。以往研究表明，这些组织中含有多巴胺刺激的腺苷酸环化酶（AC）。此外，我们现在报告听觉皮质中存在多巴胺敏感的腺苷酸环化酶。LSD和三甲氧苯乙胺可刺激ALC及听觉皮质的AC，而相同药物对FC、尾状核及视网膜的活性无刺激作用。与刺激的区域特异性相反，LSD能够拮抗所有检测脑区中多巴胺刺激的活性。LSD和三甲氧苯乙胺对ALC匀浆的AC产生相似的最大刺激（约70%），但LSD的半数有效浓度（EC50，0.43微摩尔）约为三甲氧苯乙胺（4.5微摩尔）的十分之一。听觉皮质酶也观察到类似的相对效价。虽然甲基苯丙胺比LSD弱得多，但它也对ALC的AC产生剂量依赖性刺激。致幻剂的激动剂和拮抗剂作用似乎都涉及与多巴胺受体的相互作用；LSD或甲基苯丙胺刺激的ALC活性可被多巴胺拮抗剂氟哌啶醇和氟奋乃静阻断，但不能被α受体阻滞剂酚妥拉明阻断。发现LSD在ALC和FC中对多巴胺的拮抗作用是竞争性的，三甲氧苯乙胺是一种有效的拮抗剂，但比LSD弱。此外，LSD不抑制组胺或鸟苷5′-三磷酸（Gpp(NH)p）刺激的FC活性。有人提出，致幻剂仅在灵长类动物大脑的某些区域产生多巴胺激动作用，这可能为LSD、三甲氧苯乙胺和甲基苯丙胺在灵长类动物中的至少一些行为效应提供了基础。
