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Psilocybin-induced stimulus control in the rat.

J C Winter¹, K C Rice, D J Amorosi

¹Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, 102 Farber Hall, Buffalo, NY 14214-3000, USA. jcwinter@buffalo.edu

Pharmacology, Biochemistry, and Behavior

|August 11, 2007

Summary

Psilocybin

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Area of Science:

Neuroscience
Pharmacology
Psychopharmacology

Background:

Psilocybin is a psychedelic compound, but the specific receptors it acts on for its effects are not fully understood.
Research into the pharmacological basis of psilocybin's discriminative stimulus properties in animal models is limited.

Purpose of the Study:

To investigate the role of specific neurotransmitter receptors in mediating the stimulus effects of psilocybin in rats.
To determine the contribution of serotonin 5-HT(2A) and dopamine D(2) receptors to psilocybin's discriminative stimulus.

Main Methods:

Rats were trained to discriminate psilocybin from a saline vehicle.
The effects of selective receptor antagonists (M100907, WAY-100635, remoxipride) on psilocybin discrimination were assessed.
Generalization tests with other psychoactive compounds were conducted.

Main Results:

The 5-HT(2A) receptor antagonist M100907 partially blocked psilocybin's effects.
The 5-HT(1A/7) antagonist WAY-100635 and the D(2) antagonist remoxipride did not significantly antagonize psilocybin.
Psilocybin generalized to DOM, LSD, psilocin, and DMT (with WAY-100635), but not PCP. LSD and MDMA partially generalized to psilocybin, blocked by M100907.

Conclusions:

Serotonin 5-HT(2A) receptor activity is a significant, though not sole, component of psilocybin's discriminative stimulus.
Unlike some related hallucinogens, psilocybin's stimulus control does not appear to involve 5-HT(1A) receptor agonism.

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