# Psilocybin restores spatial memory but not fronto-hippocampal synchrony in a rat model of Alzheimer's disease

Article · Shamsedin M

- Archive id: doi:10.1016/j.neures.2026.105117
- Published: 2026-09-10
- Venue: Neuroscience research
- DOI: https://doi.org/10.1016/j.neures.2026.105117
- PMID: 42722038
- Citations: 0
- Source URL: https://doi.org/10.1016/j.neures.2026.105117
- Provenance: europepmc

## 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 reproduced under CC-BY (article license as recorded by Europe PMC; abstract reproduced unmodified apart from markup removal)._

Topics: [Novel Psychiatric Therapeutics](https://space-kitty.com/topics/psychiatric-therapeutics)

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