Progress in Neuro-Psychopharmacology and Biological Psychiatry
October 1, 2025
Brandon Richardson, Antonio Inserra, Michael Pileggi et al.
2 citations
Psilocybin and lisuride both activate 5-HT2A receptors, but only psilocybin triggers the head twitch response (HTR) in mice, a proxy for hallucinogenic activity. In adult male C57BL/6N mice, psilocybin (0.3–3 mg/kg) inhibited serotonin neuron firing in the dorsal raphe nucleus via 5-HT2A receptors, while lisuride (0.1–0.5 mg/kg) did not. Both drugs reduced dopamine neuron firing in the substantia nigra, but lisuride's effect was more sensitive to 5-HT2A antagonism. Psilocybin elicited HTR; lisuride did not. Only high-dose lisuride reduced immobility in the forced swim test. Both drugs reduced locomotion in open field and elevated plus maze tests. Principal component analysis separated the drug effects, indicating distinct neurobiological pathways: psilocybin produces psychedelic-like, serotonin-dominant effects, while lisuride displays dopamine-linked improvements in coping 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.
The International Journal of Neuropsychopharmacology
February 1, 2025
Sofia Nasini, Sara Tidei, Benedetta Barzon et al.
Repeated low-dose psilocybin (0.05 mg/kg) given to adult male mice for 30 days was safe and well tolerated, with no effect on body weight. The treatment produced anxiolytic-like effects: mice spent more time in the light compartment of the light/dark box, showed shorter latency to choose the first arm in the T-maze, and reduced grooming in the open field. No changes were seen in the elevated plus maze, forced swim test, or sociability test. In the cued Morris water maze, psilocybin-treated mice reached the submerged platform faster across all three days and made more successful trials on days 1 and 2, suggesting possible enhancement of spatial memory and learning that requires further study.