Psilocybin does not induce the vulnerability marker HSP70 in neurons susceptible to Olney’s lesions
Ana-Maria Iorgu, Andrei-Nicolae Vasilescu, Natascha Pfeiffer, Rainer Spanagel, Anne Stephanie Mallien, Peter Gass, Dragoš Inta
European Archives of Psychiatry and Clinical Neuroscience November 7, 2023 DOI: 10.1007/s00406-023-01699-3 via OpenAlex
Summary
AI-generated from the abstractPsilocybin, unlike S-ketamine and MK-801, does not induce neuronal damage in the retrosplenial cortex of rats. Both S-ketamine and psilocybin are rapid-acting antidepressants that increase glutamate signalling and cortical hyperexcitation, but S-ketamine is known to cause neurotoxicity (Olney's lesions) in the retrosplenial cortex. Using immunohistochemical whole-brain mapping for heat shock protein 70 (HSP70) in rats, no HSP70-positive neurons were detected in the retrosplenial cortex of psilocybin-treated animals, whereas S-ketamine and MK-801 produced such markers. This suggests psilocybin may be safer for clinical use regarding neuronal damage.
Study at a glance
| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | Psilocybin S-ketamine MK-801 |
| Topics | Psilocybin |
| Keywords | Neuroscience Medicine Vulnerability computing Psychology |
| Citations | 2 |
| Key finding | Psilocybin did not induce HSP70-positive neurons in the retrosplenial cortex of rats, unlike S-ketamine and MK-801, suggesting it may be safer regarding neuronal damage. |
Abstract
Abstract S-ketamine, a N-methyl-D-aspartate receptor (NMDAR) antagonist, and psilocybin, a 5-hydroxy-tryptamine (serotonin) 2A receptor (5-HT 2A R) 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.