A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain

• DOI: 10.20944/preprints202011.0742.v1
• Publication Date: 2020-12-01T09:34:31Z
• Authors: Nakul Ravi Raval; Annette Johansen; Lene Lundgaard Do...; Nídia Fernandez Ros; Brice Ozenne; Hanne Demant Hansen; Gitte Moos Knudsen
• Keywords: Psilocybin; Synaptogenesis

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could linked to increased synaptogenesis down-regulation cerebral 5-HT2AR. Here, we investigate if psilocybin changes synaptic vesicle protein (SV2A) 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg or saline intravenously. Twelve (n=6/intervention) were euthanized one day post-injection, while remaining twelve seven days post-injection (n=6/intervention). We performed autoradiography on hippocampus prefrontal cortex (PFC) sections [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) [3H]Cimbi-36 agonist). One post injection, observed 4.4% higher hippocampal SV2A lowered PFC (-15.21% -50.19%). These differences statistically significant for all radioligands only. Seven post-intervention, there was still significantly (+9.24%) (+6.1%) whereas no longer any density. Our findings suggest that psilocybin’s actions are persistent possibly also an acute decrease