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 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.
Winter
J C
JC
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA. jcwinter@buffalo.edu
Rice
K C
KC
Amorosi
D J
DJ
Rabin
R A
RA
D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects; D003627:Data Interpretation, Statistical; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005795:Generalization, Stimulus / Q000187:drug effects*; D006213:Hallucinogens / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008238:Lysergic Acid Diethylamide / Q000494:pharmacology; D008297:Male; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology; D010622:Phencyclidine / Q000494:pharmacology; D011562:Psilocybin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344; D012055:Reinforcement Schedule
D006213:Hallucinogens; D011562:Psilocybin; D008238:Lysergic Acid Diethylamide; D010622:Phencyclidine; D018817:N-Methyl-3,4-methylenedioxyamphetamine
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