迷幻化合物具有潜在的快速,持久的抗焦虑药,抗抑郁和抗炎作用。我们调查了迷幻化合物(R)-2,5-二甲氧基-4-碘苯丙胺[(R)-DOI],选择性5-HT2A受体部分激动剂,降低暴露于反复社交攻击的雄性小鼠的压力相关行为。此外,我们探讨了这些行为变化与[(R)-DOI]抗炎特性相关的可能性.对动物进行应激替代模型(SAM),一种不可避免的社会压力范式,其中动物发展出反应性应对策略-与社会侵略者一起留在SAM竞技场(Stay)中,或动态启动的压力应对策略,涉及利用逃生孔(Escape)来避免侵略。表达这些行为表型的小鼠表现出类似于其他社会侵略模型中的行为,这些模型将动物分为易受攻击的(如Stay)或有压力的(如Escape)组。已被证明对社会压力有明显的炎症反应。这些结果表明,Stay动物具有增强的细胞因子基因表达,与未应激的对照小鼠相比,Stay和Escape小鼠均表现出炎性细胞因子肿瘤坏死因子-α(TNFα)的血浆和神经浓度。此外,这些结果表明,单次施用(R)-DOI以低剂量停留动物,可以增加压力应对策略,例如增加对逃生路线的关注,促进逃避行为,并减少SAM中社交激进互动期间的冻结。较低的单剂量(R)-DOI,除了改变行为以暗示抗焦虑作用外,还伴随着降低炎性细胞因子TNFα的血浆和边缘脑水平。
Psychedelic compounds have potentially rapid, long-lasting anxiolytic, antidepressive and anti-inflammatory effects. We investigated whether the psychedelic compound (R)-2,5-dimethoxy-4-iodoamphetamine [(R)-DOI], a selective 5-HT2A receptor partial agonist, decreases stress-related behavior in male mice exposed to repeated social aggression. Additionally, we explored the likelihood that these behavioral changes are related to anti-inflammatory properties of [(R)-DOI]. Animals were subjected to the Stress Alternatives Model (SAM), an escapable social stress paradigm in which animals develop reactive coping strategies - remaining in the SAM arena (Stay) with a social aggressor, or dynamically initiated stress coping strategies that involve utilizing the escape holes (Escape) to avoid aggression. Mice expressing these behavioral phenotypes display behaviors like those in other social aggression models that separate animals into stress-vulnerable (as for Stay) or stress-resilient (as for Escape) groups, which have been shown to have distinct inflammatory responses to social stress. These results show that Stay animals have heightened cytokine gene expression, and both Stay and Escape mice exhibit plasma and neural concentrations of the inflammatory cytokine tumor necrosis factor-α (TNFα) compared to unstressed control mice. Additionally, these results suggest that a single administration of (R)-DOI to Stay animals in low doses, can increase stress coping strategies such as increasing attention to the escape route, promoting escape behavior, and reducing freezing during socially aggressive interaction in the SAM. Lower single doses of (R)-DOI, in addition to shifting behavior to suggest anxiolytic effects, also concomitantly reduce plasma and limbic brain levels of the inflammatory cytokine TNFα.