- Single psilocybin dose restored ICV-STZ-induced spatial memory and learning deficits, normalising Y-maze alternation and Barnes maze escape latency.
- Psilocybin significantly reduced forced swim immobility, indicating decreased depressive-like behaviour, without altering anxiety-like behaviour or locomotion.
- Fronto-hippocampal synchrony and most electrophysiological metrics unchanged; behavioural rescue lacked a robust electrophysiological signature, requiring replication in larger cohorts robust to artefacts.
Neurosci Res. 2026 Sep 10:105117. doi: 10.1016/j.neures.2026.105117. Online ahead of print.
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 (2.5mg/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.
PMID:42722038 | DOI:10.1016/j.neures.2026.105117
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