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Published on: July 9, 2016
Enhancing cGMP signaling with psilocybin reduces head twitch and restructures the synaptic proteome while maintaining
Gabriele Floris1, Sarah J Jefferson1, Jocelyne Rondeau1
1Yale University Department of Psychiatry, New Haven, CT, USA.
Abstract:
Psilocybin produces antidepressant effects, but perceptual effects limit tolerability. We hypothesized that enhancing cGMP signaling with a phosphodiesterase-9 inhibitor (PDE9i) would diminish a rodent behavioral readout of 5-HT₂AR activation, while preserving antidepressant-like effects. PDE9i attenuated psilocybin-induced head-twitch while maintaining the antidepressant-like response. PDE9i-psilocybin reduced 5-HT₂AR-related pathways while enhancing synaptogenesis signaling.
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