Psilocybin Does Not Induce the Vulnerability Marker HSP70 in Neurons Susceptible to Olney's Lesions

Overview

Journal Eur Arch Psychiatry Clin Neurosci

Specialties Neurology
Psychiatry

Date 2023 Nov 7

PMID 37934233

Authors

Ana-Maria Iorgu

Andrei-Nicolae Vasilescu

Natascha Pfeiffer

Rainer Spanagel

Anne Stephanie Mallien

Dragos Inta

Peter Gass

Affiliations

Soon will be listed here.

Abstract

S-ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, and psilocybin, a 5-hydroxy-tryptamine (serotonin) 2A receptor (5-HTR) agonist, are reported as effective rapid-acting antidepressants. Both compounds increase glutamate signalling and evoke cortical hyperexcitation. S-ketamine induces neurotoxicity especially in the retrosplenial cortex (Olney's lesions). Whether psilocybin produces similar neurotoxic effects has so far not been investigated. We performed an immunohistochemical whole-brain mapping for heat shock protein 70 (HSP70) in rats treated with psilocybin, S-ketamine, and MK-801. In contrast to S-ketamine- and MK-801-treated animals, we did not detect any HSP70-positive neurons in retrosplenial cortex of rats treated with psilocybin. Our results suggest that psilocybin might be safer for clinical use compared to S-ketamine regarding neuronal damage.

Citing Articles

Are "mystical experiences" essential for antidepressant actions of ketamine and the classic psychedelics?.

Hashimoto K Eur Arch Psychiatry Clin Neurosci. 2024; .

PMID: 38411629 DOI: 10.1007/s00406-024-01770-7.

References

McCulloch D, Korsbak Madsen M, Stenbaek D, Kristiansen S, Ozenne B, Jensen P . Lasting effects of a single psilocybin dose on resting-state functional connectivity in healthy individuals. J Psychopharmacol. 2021; 36(1):74-84. PMC: 8801642. DOI: 10.1177/02698811211026454. View

Korsbak Madsen M, MacDonald Fisher P, Stenbaek D, Kristiansen S, Burmester D, Lehel S . A single psilocybin dose is associated with long-term increased mindfulness, preceded by a proportional change in neocortical 5-HT2A receptor binding. Eur Neuropsychopharmacol. 2020; 33:71-80. DOI: 10.1016/j.euroneuro.2020.02.001. View

De Gregorio D, Aguilar-Valles A, Preller K, Heifets B, Hibicke M, Mitchell J . Hallucinogens in Mental Health: Preclinical and Clinical Studies on LSD, Psilocybin, MDMA, and Ketamine. J Neurosci. 2020; 41(5):891-900. PMC: 7880300. DOI: 10.1523/JNEUROSCI.1659-20.2020. View

Morris P, Burke R, Sharma A, Lynch D, Lemke-Boutcher L, Mathew S . A comparison of the pharmacokinetics and NMDAR antagonism-associated neurotoxicity of ketamine, (2R,6R)-hydroxynorketamine and MK-801. Neurotoxicol Teratol. 2021; 87:106993. PMC: 8440345. DOI: 10.1016/j.ntt.2021.106993. View

Burmester D, Korsbak Madsen M, Szabo A, Aripaka S, Stenbaek D, Frokjaer V . Subacute effects of a single dose of psilocybin on biomarkers of inflammation in healthy humans: An open-label preliminary investigation. Compr Psychoneuroendocrinol. 2022; 13:100163. PMC: 9761602. DOI: 10.1016/j.cpnec.2022.100163. View

McCulloch D, Grzywacz M, Korsbak Madsen M, Jensen P, Ozenne B, Armand S . Psilocybin-Induced Mystical-Type Experiences are Related to Persisting Positive Effects: A Quantitative and Qualitative Report. Front Pharmacol. 2022; 13:841648. PMC: 8959755. DOI: 10.3389/fphar.2022.841648. View

Moliner R, Girych M, Brunello C, Kovaleva V, Biojone C, Enkavi G . Psychedelics promote plasticity by directly binding to BDNF receptor TrkB. Nat Neurosci. 2023; 26(6):1032-1041. PMC: 10244169. DOI: 10.1038/s41593-023-01316-5. View

Carhart-Harris R, Bolstridge M, Rucker J, Day C, Erritzoe D, Kaelen M . Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016; 3(7):619-27. DOI: 10.1016/S2215-0366(16)30065-7. View

Wojtas A, Bysiek A, Wawrzczak-Bargiela A, Szych Z, Majcher-Maslanka I, Herian M . Effect of Psilocybin and Ketamine on Brain Neurotransmitters, Glutamate Receptors, DNA and Rat Behavior. Int J Mol Sci. 2022; 23(12). PMC: 9224489. DOI: 10.3390/ijms23126713. View

10.

Choudhury D, Autry A, Tolias K, Krishnan V . Ketamine: Neuroprotective or Neurotoxic?. Front Neurosci. 2021; 15:672526. PMC: 8461018. DOI: 10.3389/fnins.2021.672526. View

11.

Raval N, Johansen A, Donovan L, Fernandez Ros N, Ozenne B, Hansen H . A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT Receptor Density in the Pig Brain. Int J Mol Sci. 2021; 22(2). PMC: 7830000. DOI: 10.3390/ijms22020835. View

12.

Huang J, Pham M, Panenka W, Honer W, Barr A . Chronic Treatment With Psilocybin Decreases Changes in Body Weight in a Rodent Model of Obesity. Front Psychiatry. 2022; 13:891512. PMC: 9157591. DOI: 10.3389/fpsyt.2022.891512. View

13.

Herian M, Wojtas A, Mackowiak M, Wawrzczak-Bargiela A, Solarz A, Bysiek A . Neurotoxicological profile of the hallucinogenic compound 25I-NBOMe. Sci Rep. 2022; 12(1):2939. PMC: 8861095. DOI: 10.1038/s41598-022-07069-8. View

14.

Madsen M, Fisher P, Burmester D, Dyssegaard A, Stenbaek D, Kristiansen S . Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels. Neuropsychopharmacology. 2019; 44(7):1328-1334. PMC: 6785028. DOI: 10.1038/s41386-019-0324-9. View

15.

Moon I, Park I, Schenker L, Kennedy M, Moon J, Jin I . Presence of both constitutive and inducible forms of heat shock protein 70 in the cerebral cortex and hippocampal synapses. Cereb Cortex. 2001; 11(3):238-48. DOI: 10.1093/cercor/11.3.238. View

16.

Li Q, Clark S, Lewis D, Wilson W . NMDA receptor antagonists disinhibit rat posterior cingulate and retrosplenial cortices: a potential mechanism of neurotoxicity. J Neurosci. 2002; 22(8):3070-80. PMC: 6757533. DOI: 20026304. View

17.

Mason N, Kuypers K, Muller F, Reckweg J, Tse D, Toennes S . Me, myself, bye: regional alterations in glutamate and the experience of ego dissolution with psilocybin. Neuropsychopharmacology. 2020; 45(12):2003-2011. PMC: 7547711. DOI: 10.1038/s41386-020-0718-8. View

18.

Kadriu B, Greenwald M, Henter I, Gilbert J, Kraus C, Park L . Ketamine and Serotonergic Psychedelics: Common Mechanisms Underlying the Effects of Rapid-Acting Antidepressants. Int J Neuropsychopharmacol. 2020; 24(1):8-21. PMC: 7816692. DOI: 10.1093/ijnp/pyaa087. View

19.

Farber N, Hanslick J, Kirby C, McWilliams L, Olney J . Serotonergic agents that activate 5HT2A receptors prevent NMDA antagonist neurotoxicity. Neuropsychopharmacology. 1997; 18(1):57-62. DOI: 10.1016/S0893-133X(97)00127-9. View

20.

Gass P, Prior P, Kiessling M . Correlation between seizure intensity and stress protein expression after limbic epilepsy in the rat brain. Neuroscience. 1995; 65(1):27-36. DOI: 10.1016/0306-4522(95)92049-p. View