Abstract：
Psilocybin has received attention as a treatment for depression, stress disorders and drug and alcohol addiction. To help determine the mechanisms underlying its therapeutic effects, here we examined acute effects of a range of behaviourally relevant psilocybin doses (0.1-3 mg/kg SC) on regional expression of Fos, the protein product of the immediate early gene, c-fos in brain areas involved in stress, reward and motivation in male rats. We also determined the cellular phenotypes activated by psilocybin, in a co-labeling analysis with NeuN, a marker of mature neurons, or Olig1, a marker of oligodendrocytes. In adult male Sprague-Dawley rats, psilocybin increased Fos expression dose dependently in several brain regions, including the frontal cortex, nucleus accumbens, central and basolateral amygdala and locus coeruleus. These effects were most marked in the central amygdala. Double labeling experiments showed that Fos was expressed in both neurons and oligodendrocytes. These results extend previous research by determining Fos expression in multiple brain areas at a wider psilocybin dose range, and the cellular phenotypes expressing Fos. The data also highlight the amygdala, especially the central nucleus, a key brain region involved in emotional processing and learning and interconnected with other brain areas involved in stress, reward and addiction, as a potentially important locus for the therapeutic effects of psilocybin. Overall, the present findings suggest that the central amygdala may be an important site through which the initial brain activation induced by psilocybin is translated into neuroplastic changes, locally and in other regions that underlie its extended therapeutic effects.
摘要：
Psilocybin作为抑郁症的治疗方法受到关注，压力障碍和药物和酒精成瘾。为了帮助确定其治疗效果的潜在机制，在这里，我们检查了一系列行为相关裸盖菇素剂量（0.1-3mg/kgSC）对Fos区域表达的急性影响，立即早期基因的蛋白质产物，涉及压力的大脑区域的c-fos，雄性大鼠的奖励和动机。我们还确定了由psilocybin激活的细胞表型，在与NeuN的共标记分析中，成熟神经元的标记，或Olig1，少突胶质细胞的标记。在成年雄性Sprague-Dawley大鼠中，psilocybin在几个大脑区域剂量依赖性地增加Fos表达，包括额叶皮层,伏隔核,中央和基底外侧杏仁核和蓝斑。这些作用在中央杏仁核中最为明显。双标记实验表明，Fos在神经元和少突胶质细胞中均有表达。这些结果通过在更宽的psilocybin剂量范围内确定多个大脑区域的Fos表达来扩展先前的研究，和表达Fos的细胞表型。数据还突出了杏仁核，尤其是中央核,参与情绪处理和学习的关键大脑区域，与参与压力的其他大脑区域相互关联，奖励和成瘾，作为psilocybin治疗效果的潜在重要位点。总的来说,目前的研究结果表明，中央杏仁核可能是一个重要的位点，通过它，psilocybin诱导的初始大脑激活被转化为神经可塑性变化，在当地和其他地区，作为其扩展治疗效果的基础。
