Psilocybin does not induce the vulnerability marker HSP70 in neurons susceptible to Olney's lesions

Eur Arch Psychiatry Clin Neurosci. 2024 Jun;274(4):1013-1019. doi: 10.1007/s00406-023-01699-3. Epub 2023 Nov 7.

Abstract

S-ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, and psilocybin, a 5-hydroxy-tryptamine (serotonin) 2A receptor (5-HT2AR) 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.

Keywords: Antidepressant; HSP70; Ketamine; Olney’s lesions; Psilocybin.

MeSH terms

  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Dizocilpine Maleate / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • HSP70 Heat-Shock Proteins* / drug effects
  • HSP70 Heat-Shock Proteins* / metabolism
  • Hallucinogens / pharmacology
  • Ketamine* / pharmacology
  • Male
  • Neurons* / drug effects
  • Neurons* / metabolism
  • Psilocybin* / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Psilocybin
  • HSP70 Heat-Shock Proteins
  • Ketamine
  • Dizocilpine Maleate
  • Hallucinogens
  • Excitatory Amino Acid Antagonists