Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.
Magdalena Kolasa, Agnieszka Nikiforuk, Agata Korlatowicz, Joanna Solich, Agnieszka Potasiewicz, Marta Dziedzicka-Wasylewska, Ryszard Bugno, Adam S. Hogendorf, Andrzej J. Bojarski, Agata Faron-Górecka
Psychopharmacology July 4, 2024 DOI: 10.1007/s00213-024-06644-3 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational cohort Peer reviewed |
|---|---|
| Population | Wistar-Kyoto rats and Wistar rats |
| Intervention | Psilocybin |
| Duration | Post-acute and extended assessments after a single administration |
| Topics | Depression Neuroplasticity Psilocybin |
| Keywords | Long-term effect Social interaction Weight gain Wistar kyoto rats Hallucinogens Psychedelics Depression treatment antidepressants Mood disorders Mental health Neuroplasticity brain plasticity Neural adaptation Synap |
| Citations | 18 |
| Key findings | Psilocybin produced antidepressant and pro-social effects in both rat strains, with strain-specific variations in BDNF signaling and Arc expression modulation in Wistar-Kyoto rats. |
Abstract
Our study aimed to unravel the unknown mechanisms behind the exceptional efficacy of Psilocybin (PSI) in treating treatment-resistant depression (TRD). Focusing on Wistar-Kyoto (WKY) rats with a TRD phenotype and Wistar (WIS) rats as a normative comparison, we investigated behavioral and neuroplasticity-related responses to PSI, striving to shed light on the distinctive features of its antidepressant effects. We set out to assess the behavioral impact of acute and prolonged PSI administration on WKY and WIS rats, employing Novel Object Recognition (NORT), Social Interaction (SI), and Forced Swimming Test (FST). Our secondary objectives involved exploring strain-specific alterations in neuroplasticity-related parameters, including brain-derived neurotrophic factor (BDNF) and activity-regulated cytoskeleton-associated protein (Arc). Conducting post-acute and extended assessments after a single PSI administration, we applied behavioral tests and biochemical analyses to measure serum BDNF levels and neuroplasticity-related parameters in the prefrontal cortex. Statistical analyses were deployed to discern significant differences between the rat strains and assess the impact of PSI on behavioral and biochemical outcomes. Our findings uncovered significant behavioral disparities between WKY and WIS rats, indicating passive behavior and social withdrawal in the former. PSI demonstrated pronounced pro-social and antidepressant effects in both strains, each with its distinctive temporal trajectory. Notably, we identified strain-specific variations in BDNF-related signaling and observed the modulation of Arc expression in WKY rats. Our study delineated mood-related behavioral nuances between WKY and WIS rat strains, underscoring the antidepressant and pro-social properties of PSI in both groups. The distinct temporal patterns of observed changes and the identified strain-specific neuroplasticity alterations provide valuable insights into the TRD phenotype and the mechanisms underpinning the efficacy of PSI.