Psilocybin-induced stimulus control in the rat.
Pharmacology, biochemistry, and behavior – October 01, 2007
Source: PubMed
Summary
Rats trained to recognize psilocybin revealed its unique brain effects involve a complex interplay of receptors. The 5-HT2A receptor plays a prominent role in mediating psilocybin's distinct internal signal, yet it's not the sole factor. Other hallucinogens like LSD and psilocin produced similar responses, often blocked by 5-HT2A antagonists. Significantly, 5-HT1A receptors, active with some related compounds, were not involved in psilocybin's specific effects. This advances our understanding of psilocybin's precise mechanisms.
Abstract
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.