Marona-Lewicka Danuta, Nichols David E
Department of Medicinal Chemistry and Molecular Pharmacology, School of Pharmacy and Pharmaceutical Sciences, RHPH, 575 Stadium Mall Dr. Purdue University, West Lafayette, IN 47907-2091, United States.
Pharmacol Biochem Behav. 2007 Oct;87(4):453-61. doi: 10.1016/j.pbb.2007.06.001. Epub 2007 Jun 14.
Activation of 5-HT(2A) receptors is thought to mediate the hallucinogenic effects of LSD. Nevertheless, in a previous report we provided evidence that a delayed temporal phase of the behavioral pharmacology of LSD is mediated by D(2)-like dopamine receptor stimulation. In this study rats were trained to discriminate LSD with either a 30 min preinjection time (LSD-30, N=12) or a 90 min preinjection time (LSD-90, N=13) from saline, using a two-lever, food-reinforced operant conditioning task. We then tested a large number of agonists and antagonists belonging to distinct pharmacological classes in these animals. As anticipated, classical hallucinogens such as psilocin and mescaline substituted only in LSD-30 rats, and not in LSD-90 rats. The dopamine receptor agonists ABT-724, aripiprazole, dihydrexidine, WAY 100635, and SKF 38393, fully or partially mimicked LSD-90, but not LSD-30. The results reported here support and extend our previous conclusion that the delayed temporal effects of LSD are mediated by activation of a dopaminergic system.
5-HT(2A)受体的激活被认为介导了麦角酸二乙酰胺（LSD）的致幻作用。然而，在之前的一份报告中，我们提供了证据表明，LSD行为药理学的延迟时相是由D(2)样多巴胺受体刺激介导的。在本研究中，使用双杠杆、食物强化的操作性条件反射任务，训练大鼠在预注射时间为30分钟（LSD-30，N = 12）或90分钟（LSD-90，N = 13）的情况下，区分LSD和生理盐水。然后，我们在这些动物中测试了大量属于不同药理学类别的激动剂和拮抗剂。正如预期的那样，经典致幻剂如裸盖菇素和三甲氧苯乙胺仅在LSD-30大鼠中替代，而在LSD-90大鼠中则不然。多巴胺受体激动剂ABT-724、阿立哌唑、二氢麦角隐亭、WAY 100635和SKF 38393完全或部分模拟了LSD-90，但没有模拟LSD-30。此处报告的结果支持并扩展了我们之前的结论，即LSD的延迟时相效应是由多巴胺能系统的激活介导的。
