# A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT 2A Receptor Density in the Pig Brain

Article · Raval NR, Johansen A, Donovan LL, Ros NF, Ozenne B, Hansen HD, Knudsen GM

- Archive id: doi:10.3390/ijms22020835
- Published: 2021-01-15
- Venue: International journal of molecular sciences
- DOI: https://doi.org/10.3390/ijms22020835
- PMID: 33467676
- PMCID: PMC7830000
- Citations: 170
- Source URL: https://doi.org/10.3390/ijms22020835
- PDF: https://europepmc.org/articles/PMC7830000/pdf
- Provenance: europepmc

## Abstract

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT 2A R) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT 2A R. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT 2A R density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n = 6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n = 6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with \[ 3 H\]UCB-J (SV2A), \[ 3 H\]MDL100907 (5-HT 2A R antagonist) and \[ 3 H\]Cimbi-36 (5-HT 2A R agonist). One day post psilocybin injection, we observed 4.42% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT 2A R density (-15.21% to -50.19%). These differences were statistically significant in the hippocampus for all radioligands and in the PFC for \[ 3 H\]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in the hippocampus (+9.24%) and the PFC (+6.10%), whereas there were no longer any differences in 5-HT 2A R density. Our findings suggest that psilocybin causes increased persistent synaptogenesis and an acute decrease in 5-HT 2A R density, which may play a role in psilocybin's antidepressive effects.

_Abstract reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Novel Psychiatric Therapeutics](https://space-kitty.com/topics/psychiatric-therapeutics)

---
Space Kitty Archive · https://space-kitty.com · API: https://space-kitty.com/api/v1 · MCP: https://space-kitty.com/mcp · Premium: $0.20/request via x402 (Base Sepolia (testnet)). Metadata: arXiv (CC0), OpenAlex (CC0), Europe PMC (CC BY/CC0 works), ClinicalTrials.gov.