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Article

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

1
Neurobiology Research Unit, Copenhagen University Hospital Rigshospitalet, 2100 Copenhagen, Denmark
2
Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark
3
Department of Public Health, Section of Biostatistics, Faculty of Health and Medical Sciences, University of Copenhagen, 1014 Copenhagen, Denmark
4
A. A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(2), 835; https://doi.org/10.3390/ijms22020835
Received: 3 December 2020 / Revised: 11 January 2021 / Accepted: 12 January 2021 / Published: 15 January 2021
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 be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR 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 [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) and [3H]Cimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.42% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (−15.21% to −50.19%). These differences were statistically significant in the hippocampus for all radioligands and in the PFC for [3H]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-HT2AR density. Our findings suggest that psilocybin causes increased persistent synaptogenesis and an acute decrease in 5-HT2AR density, which may play a role in psilocybin’s antidepressive effects. View Full-Text
Keywords: psilocybin; psychedelics; neuroplasticity; SV2A; 5-HT2A; depression; autoradiography; functional-selectivity psilocybin; psychedelics; neuroplasticity; SV2A; 5-HT2A; depression; autoradiography; functional-selectivity
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MDPI and ACS Style

Raval, N.R.; Johansen, A.; Donovan, L.L.; Ros, N.F.; Ozenne, B.; Hansen, H.D.; Knudsen, G.M. A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain. Int. J. Mol. Sci. 2021, 22, 835. https://doi.org/10.3390/ijms22020835

AMA Style

Raval NR, Johansen A, Donovan LL, Ros NF, Ozenne B, Hansen HD, Knudsen GM. A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain. International Journal of Molecular Sciences. 2021; 22(2):835. https://doi.org/10.3390/ijms22020835

Chicago/Turabian Style

Raval, Nakul R., Annette Johansen, Lene L. Donovan, Nídia F. Ros, Brice Ozenne, Hanne D. Hansen, and Gitte M. Knudsen 2021. "A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain" International Journal of Molecular Sciences 22, no. 2: 835. https://doi.org/10.3390/ijms22020835

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