Sakashita Yuichi, Abe Kenji, Katagiri Nobuyuki, Kambe Toshie, Saitoh Toshiaki, Utsunomiya Iku, Horiguchi Yoshie, Taguchi Kyoji
Department of Medicinal Pharmacology, Showa Pharmaceutical University.
Biol Pharm Bull. 2015;38(1):134-8. doi: 10.1248/bpb.b14-00315. Epub 2014 Oct 24.
Psilocin (3-[2-(dimethylamino)ethyl]-1H-indol-4-ol) is a hallucinogenic component of the Mexican mushroom Psilocybe mexicana and a skeletal serotonin (5-HT) analogue. Psilocin is the active metabolite of psilocybin (3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate). In the present study, we examined the effects of systemically administered psilocin on extracellular dopamine and 5-HT concentrations in the ventral tegmental area (VTA), nucleus accumbens, and medial prefrontal cortex of the dopaminergic pathway in awake rats using in vivo microdialysis. Intraperitoneal administration of psilocin (5, 10 mg/kg) significantly increased extracellular dopamine levels in the nucleus accumbens. Psilocin did not affect the extracellular 5-HT level in the nucleus accumbens. Conversely, systemic administration of psilocin (10 mg/kg) significantly increased extracellular 5-HT levels in the medial prefrontal cortex of rats, but dopamine was decreased in this region. However, neither extracellular dopamine nor 5-HT levels in the VTA were altered by administration of psilocin. Behaviorally, psilocin significantly increased the number of head twitches. Thus, psilocin affects the dopaminergic system in the nucleus accumbens. In the serotonergic system, psilocin contribute to a crucial effect in the medial prefrontal cortex. The present data suggest that psilocin increased both the extracellular dopamine and 5-HT concentrations in the mesoaccumbens and/or mesocortical pathway.
裸盖菇素（3-[2-(二甲基氨基)乙基]-1H-吲哚-4-醇）是墨西哥蘑菇墨西哥裸盖菇中的一种致幻成分，也是一种骨架型血清素（5-HT）类似物。裸盖菇素是裸盖菇碱（3-[2-(二甲基氨基)乙基]-1H-吲哚-4-基磷酸二氢酯）的活性代谢产物。在本研究中，我们使用体内微透析技术，检测了全身给药裸盖菇素对清醒大鼠多巴胺能通路的腹侧被盖区（VTA）、伏隔核和内侧前额叶皮质细胞外多巴胺和5-HT浓度的影响。腹腔注射裸盖菇素（5、10mg/kg）可显著提高伏隔核细胞外多巴胺水平。裸盖菇素不影响伏隔核细胞外5-HT水平。相反，全身给药裸盖菇素（10mg/kg）可显著提高大鼠内侧前额叶皮质细胞外5-HT水平，但该区域多巴胺水平降低。然而，注射裸盖菇素并未改变VTA细胞外多巴胺和5-HT水平。行为学上，裸盖菇素显著增加了头部抽搐次数。因此，裸盖菇素影响伏隔核中的多巴胺能系统。在血清素能系统中，裸盖菇素在内侧前额叶皮质中发挥关键作用。目前的数据表明，裸盖菇素增加了中伏隔核和/或中皮质通路中的细胞外多巴胺和5-HT浓度。
