Winter J C, Rice K C, Amorosi D J, Rabin R A
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA.
Pharmacol Biochem Behav. 2007 Oct;87(4):472-80. doi: 10.1016/j.pbb.2007.06.003. Epub 2007 Jun 22.
Although psilocybin has been trained in the rat as a discriminative stimulus, little is known of the pharmacological receptors essential for stimulus control. In the present investigation rats were trained with psilocybin and tests were then conducted employing a series of other hallucinogens and presumed antagonists. An intermediate degree of antagonism of psilocybin was observed following treatment with the 5-HT(2A) receptor antagonist, M100907. In contrast, no significant antagonism was observed following treatment with the 5-HT(1A/7) receptor antagonist, WAY-100635, or the DA D(2) antagonist, remoxipride. Psilocybin generalized fully to DOM, LSD, psilocin, and, in the presence of WAY-100635, DMT while partial generalization was seen to 2C-T-7 and mescaline. LSD and MDMA partially generalized to psilocybin and these effects were completely blocked by M-100907; no generalization of PCP to psilocybin was seen. The present data suggest that psilocybin induces a compound stimulus in which activity at the 5-HT(2A) receptor plays a prominent but incomplete role. In addition, psilocybin differs from closely related hallucinogens such as 5-MeO-DMT in that agonism at 5-HT(1A) receptors appears to play no role in psilocybin-induced stimulus control.
尽管在大鼠中已将裸盖菇素训练为一种辨别性刺激，但对于刺激控制所必需的药理受体却知之甚少。在本研究中，用裸盖菇素对大鼠进行训练，然后使用一系列其他致幻剂和假定的拮抗剂进行测试。用5-HT(2A)受体拮抗剂M100907处理后，观察到对裸盖菇素的拮抗作用处于中等程度。相比之下，用5-HT(1A/7)受体拮抗剂WAY-100635或多巴胺D(2)拮抗剂瑞莫必利处理后，未观察到明显的拮抗作用。裸盖菇素能完全泛化到2,5-二甲氧基-4-甲基苯丙胺（DOM）、麦角酸二乙胺（LSD）、脱磷酸裸盖菇素（psilocin），并且在存在WAY-100635的情况下能泛化到N,N-二甲基色胺（DMT），而对2C-T-7和三甲氧苯乙胺（mescaline）则出现部分泛化。LSD和摇头丸（MDMA）能部分泛化到裸盖菇素，并且这些效应被M-100907完全阻断；未观察到苯环己哌啶（PCP）对裸盖菇素的泛化。目前的数据表明，裸盖菇素诱导一种复合刺激，其中5-HT(2A)受体的活性起着突出但不完整的作用。此外，裸盖菇素与密切相关的致幻剂如5-甲氧基-N,N-二甲基色胺（5-MeO-DMT）不同，因为5-HT(1A)受体的激动作用似乎在裸盖菇素诱导的刺激控制中不起作用。
