Kolasa Magdalena, Nikiforuk Agnieszka, Korlatowicz Agata, Solich Joanna, Potasiewicz Agnieszka, Dziedzicka-Wasylewska Marta, Bugno Ryszard, Hogendorf Adam, Bojarski Andrzej, Faron-Górecka Agata
Department of Pharmacology, Maj Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland.
Department of Behavioral Neuroscience & Drug Development, Maj Institute of Pharmacology Polish Academy of Sciences, Kraków, Poland.
Psychopharmacology (Berl). 2024 Jul 4. doi: 10.1007/s00213-024-06644-3.
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.
我们的研究旨在揭示裸盖菇素（PSI）在治疗难治性抑郁症（TRD）方面卓越疗效背后的未知机制。以具有TRD表型的Wistar-Kyoto（WKY）大鼠和作为正常对照的Wistar（WIS）大鼠为研究对象，我们研究了对PSI的行为和神经可塑性相关反应，力求阐明其抗抑郁作用的独特特征。
我们着手评估急性和长期给予PSI对WKY和WIS大鼠的行为影响，采用新物体识别（NORT）、社交互动（SI）和强迫游泳试验（FST）。我们的次要目标包括探索神经可塑性相关参数的品系特异性变化，包括脑源性神经营养因子（BDNF）和活性调节细胞骨架相关蛋白（Arc）。
在单次给予PSI后进行急性和延长评估，我们应用行为测试和生化分析来测量血清BDNF水平和前额叶皮质中与神经可塑性相关的参数。采用统计分析来辨别大鼠品系之间的显著差异，并评估PSI对行为和生化结果的影响。
我们的研究结果揭示了WKY和WIS大鼠之间存在显著的行为差异，表明前者存在被动行为和社交退缩。PSI在两种品系中均表现出显著的亲社会和抗抑郁作用，每种作用都有其独特的时间轨迹。值得注意的是，我们确定了与BDNF相关信号传导的品系特异性差异，并观察到WKY大鼠中Arc表达的调节。
我们的研究描绘了WKY和WIS大鼠品系之间与情绪相关的行为细微差别，强调了PSI在两组中的抗抑郁和亲社会特性。观察到的变化的独特时间模式以及确定的品系特异性神经可塑性改变为TRD表型以及PSI疗效背后的机制提供了有价值的见解。
