Psilocybin Restores Spatial Memory but Not Fronto-Hippocampal Synchrony in a Rat Model of Alzheimer's Disease
Neuroscience Research September 1, 2026 DOI: 10.1016/j.neures.2026.105117 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Randomized controlled animal experiment Peer reviewed |
|---|---|
| Population | Male rats with intracerebroventricular streptozotocin-induced neurotoxicity |
| Interventions | Psilocybin intracerebroventricular streptozotocin |
| Dose | 2.5 mg/kg |
| Measures | Y-maze, novel object recognition, Barnes maze, elevated plus maze, forced swim test, resting-state local field potentials |
| Topics | Psilocybin |
| Key findings | A single 2.5 mg/kg psilocybin dose reversed streptozotocin-induced 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, a dissociation the authors say warrants replication in larger cohorts. |
Abstract
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.