Department of Psychiatry and Psychotherapy, Research Group Animal Models in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, University of Heidelberg, J5, 68159, Mannheim, Germany.
2 papers in the library · 2 citations · publishing 2023-2026
Psilocybin, 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.
Classical and rapid-acting antidepressants alter how the brain responds to acute stress through different molecular programs. In mice exposed to swim stress, imipramine dampened stress-induced neural activation in the cortex and striatum, while ketamine preserved it. Hippocampal activation remained robust and unaffected by either drug. BDNF expression changed only in the striatum, where imipramine reduced the stress-related increase. Both drugs similarly promoted active coping behaviors, but through distinct mechanisms. The findings suggest that cortical and striatal transcriptional signatures differentiate classical from rapid-acting antidepressant action, though human studies are needed to confirm clinical relevance.