Hallucinogenic indoleamines: Preferential action upon presynaptic serotonin receptors.

Previously, d-lysergic acid diethylamide was found to have a more powerful inhibitory action upon serotonergic (raphe) neurons than upon neurons in areas receiving an identified serotonergic input (e. g., amygdala, ventral lateral geniculate). In the present studies, using microiontophoretic techniques, the relative potencies of 3 indoleamine hallucinogens, psilocin, DMT, and bufotenine were tested upon 5HT neurons in the raphe (presynaptic neurons) and postsynaptic neurons in the ventral lateral geniculate and amygdala of the rat. Psilocin showed the greatest preferential inhibitory effect upon raphe as compared to postsynaptic neurons. DMT was intermdeiate and bufotenine had the least differential activity. This rank ordering correlates with the relative hallucinogenic potencies of these compounds: psilocin greater than DMT greater than bufotenine. The results support the hypothesis that low doses of indoleamine halluciogens act preferentially upon presynaptic serotonin receptors to inhibit raphe neurons, thus releasing postsynaptic neurons from a tonic inhibitory serotonergic influence.