363. DIFFERENTIAL EFFECTS OF PSILOCYBIN AND LISURIDE ON SEROTONIN AND DOPAMINE NEURONAL ACTIVITY AND BEHAVIOR
The International Journal of Neuropsychopharmacology August 1, 2025 B. D. Richardson, Marco Pileggi, Thomas Prudhomme et al.
Psilocybin and lisuride both bind to 5-HT2A receptors, but only psilocybin produces hallucinogenic effects. In adult male mice, both drugs inhibited serotonin neuron activity in the dorsal raphe nucleus and dopamine neuron firing in the substantia nigra. A 5-HT2A antagonist blocked psilocybin's serotonin inhibition but not lisuride's, suggesting different mechanisms. Only lisuride showed an antidepressant-like effect at the highest doses. Psilocybin, but not lisuride, elicited head-twitch responses, and lisuride blocked those induced by psilocybin. Both drugs reduced locomotion. The findings indicate lisuride has antidepressant and sedative effects without hallucinogenic action, likely due to its distinct effects on serotonin and dopamine neurons.