Journal
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
Volume 87, Issue 4, Pages 472-480Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.pbb.2007.06.003
Keywords
psilocybin; drug discrimination; rat; LSD; M100907; WAY-100635; ketanserin; bufotenine; 2C-T-7; MDMA; PCP
Funding
- NIDA NIH HHS [R01 DA003385, DA 03385, R56 DA003385, R01 DA003385-18] Funding Source: Medline
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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-HT2A receptor antagonist, M100907. In contrast, no significant antagonism was observed following treatment with the 5-HT1A/7 receptor antagonist, WAY-100635, or the DAD, 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-HT2A 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-HT1A receptors appears to play no role in psilocybin-induced stimulus control. (c) 2007 Elsevier Inc. All rights reserved.
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