{"id":"doi:10.1016/j.neures.2026.105117","kind":"article","title":"Psilocybin restores spatial memory but not fronto-hippocampal synchrony in a rat model of Alzheimer's disease","authors":["Shamsedin M"],"author_count":1,"year":2026,"published":"2026-09-10","venue":"Neuroscience research","cited_by":0,"doi":"10.1016/j.neures.2026.105117","arxiv_id":null,"nct_id":null,"source_url":"https://doi.org/10.1016/j.neures.2026.105117","archive_url":"https://space-kitty.com/papers/doi:10.1016/j.neures.2026.105117","updated":null,"pmid":"42722038","pmcid":null,"openalex_id":null,"pdf_url":null,"abstract":"Background Fronto-hippocampal desynchronization is linked to cognitive decline in Alzheimer's-like pathology, but whether psilocybin can restore this dysfunction is unknown. Methods Male rats received intracerebroventricular streptozotocin (ICV-STZ) to induce neurotoxicity, followed by a single dose of psilocybin (2.5 mg/kg, the maximum tolerated dose). Spatial memory, recognition memory, spatial learning, anxiety-like behavior, and depressive-like behavior were assessed (Y-maze, novel object recognition, Barnes maze, elevated plus maze, forced swim test), alongside resting-state local field potentials from the prefrontal cortex and hippocampus. Results ICV-STZ impaired spontaneous alternation and Barnes maze learning (both p < 0.01), without affecting anxiety-like behavior or locomotion. Novel object discrimination index showed a similar but non-significant pattern (p = 0.155). Forced swim test immobility was numerically higher after ICV-STZ but not significantly different from Control (p = 0.068); psilocybin significantly reduced immobility versus STZ (p < 0.001) and normalized alternation and escape latency to control levels. Spectral power, coherence, and cross-correlation did not differ significantly among groups at most sessions and bands (p > 0.08), except one elevated mPFC-ventral hippocampal correlation in STZ animals (p = 0.029, small cohort), not replicated with psilocybin. Conclusion A single psilocybin dose reversed spatial memory and learning deficits and reduced depressive-like immobility, without altering anxiety-like behavior or locomotion, but this behavioral rescue was not accompanied by a robust electrophysiological signature. This dissociation warrants replication using larger, artifact-robust cohorts and reference-free connectivity metrics.","abstract_license":"CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)","license":"CC-BY","is_open_access":false,"retracted":false,"peer_reviewed":null,"categories":[],"details":null,"provenance":"europepmc","attribution":"Abstract of \"Psilocybin restores spatial memory but not fronto-hippocampal synchrony in a rat model of Alzheimer's disease\" by Shamsedin M, https://doi.org/10.1016/j.neures.2026.105117, used under its Creative Commons Attribution license (CC-BY); markup removed, otherwise unmodified.","topics":[{"slug":"psychiatric-therapeutics","name":"Novel Psychiatric Therapeutics","domain_slug":"neuroscience"}],"cited_in_dossiers":[]}