A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain. / Raval, Nakul Ravi; Johansen, Annette; Donovan, Lene Lundgaard; Ros, Nídia Fernandez; Ozenne, Brice; Hansen, Hanne Demant; Knudsen, Gitte Moos.

In: International Journal of Molecular Sciences, Vol. 22, No. 2, 835, 2021.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Raval, NR, Johansen, A, Donovan, LL, Ros, NF, Ozenne, B, Hansen, HD & Knudsen, GM 2021, 'A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain', International Journal of Molecular Sciences, vol. 22, no. 2, 835. https://doi.org/10.3390/ijms22020835

APA

Raval, N. R., Johansen, A., Donovan, L. L., Ros, N. F., Ozenne, B., Hansen, H. D., & Knudsen, G. M. (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(2), [835]. https://doi.org/10.3390/ijms22020835

Vancouver

Raval NR, Johansen A, Donovan LL, Ros NF, Ozenne B, Hansen HD et al. 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

Author

Raval, Nakul Ravi ; Johansen, Annette ; Donovan, Lene Lundgaard ; Ros, Nídia Fernandez ; Ozenne, Brice ; Hansen, Hanne Demant ; Knudsen, Gitte Moos. / A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain. In: International Journal of Molecular Sciences. 2021 ; Vol. 22, No. 2.

Bibtex

@article{746f3cc718d04c6a9262ba1d1068cbda,
title = "A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain",
abstract = "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{\textquoteright}s antidepressive effects.",
keywords = "5-HT2A, Autoradiography, Depression, Functional-selectivity, Neuroplasticity, Psilocybin, Psychedelics, SV2A",
author = "Raval, {Nakul Ravi} and Annette Johansen and Donovan, {Lene Lundgaard} and Ros, {N{\'i}dia Fernandez} and Brice Ozenne and Hansen, {Hanne Demant} and Knudsen, {Gitte Moos}",
year = "2021",
doi = "10.3390/ijms22020835",
language = "English",
volume = "22",
journal = "International Journal of Molecular Sciences (CD-ROM)",
issn = "1424-6783",
publisher = "M D P I AG",
number = "2",

}

RIS

TY - JOUR

T1 - A single dose of psilocybin increases synaptic density and decreases 5-HT2A receptor density in the pig brain

AU - Raval, Nakul Ravi

AU - Johansen, Annette

AU - Donovan, Lene Lundgaard

AU - Ros, Nídia Fernandez

AU - Ozenne, Brice

AU - Hansen, Hanne Demant

AU - Knudsen, Gitte Moos

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - 5-HT2A

KW - Autoradiography

KW - Depression

KW - Functional-selectivity

KW - Neuroplasticity

KW - Psilocybin

KW - Psychedelics

KW - SV2A

U2 - 10.3390/ijms22020835

DO - 10.3390/ijms22020835

M3 - Journal article

C2 - 33467676

AN - SCOPUS:85099566650

VL - 22

JO - International Journal of Molecular Sciences (CD-ROM)

JF - International Journal of Molecular Sciences (CD-ROM)

SN - 1424-6783

IS - 2

M1 - 835

ER -

ID: 256716986