ArticlePsychopharmacology2025
Unraveling psilocybin's therapeutic potential: behavioral and neuroplasticity insights in Wistar-Kyoto and Wistar male rat models of treatment-resistant depression.
Article in Psychopharmacology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Multilevel Mechanisms and Clinical Efficacy of Psilocybin in Depression Treatment: A Systematic Review.International journal of molecular sciences · 2026Pooled it
- The Wistar-Kyoto rat as a model relevant to inattentive ADHD: substrain variability and affective comorbidity.Pharmacological reports : PR · 2026Review
- Psilocybin modulates social behaviour in male and female mice in a time-dependent manner.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Long- term administration of low doses of psilocybin causes epigenetic changes in the rat medial prefrontal cortex.Psychopharmacology · 2026Article
- Fentanyl, Methamphetamine and Polysubstance Use Differentially Affect Locomotor Sensitisation and Social Behaviour in Rats: Psychedelic Treatment Reverses Social Deficits.Addiction biology · 2026Article
- Psychedelic Drugs in Mental Disorders: Current Clinical Scope and Deep Learning-Based Advanced Perspectives.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Review
- Neuroplasticity and Mechanisms of Action of Acute and Chronic Treatment with Antidepressants in Preclinical Studies.Biomedicines · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
10 authors.
Funding
Abstract
rationaleOur 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.
objectivesWe 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).
methodsConducting 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.
resultsOur 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.
conclusionsOur 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.
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