Psilocybin-induced stimulus control in the rat

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 D₂ 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.