Effect of Psilocin on Extracellular Dopamine and Serotonin Levels in the Mesoaccumbens and Mesocortical Pathway in Awake Rats

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  • Sakashita Yuichi
    Department of Medicinal Pharmacology, Showa Pharmaceutical University
  • Abe Kenji
    Department of Pharmacology, School of Pharmaceutical Sciences, Ohu University
  • Katagiri Nobuyuki
    Department of Medicinal Pharmacology, Showa Pharmaceutical University
  • Kambe Toshie
    Department of Pharmacology, Showa Pharmaceutical University
  • Saitoh Toshiaki
    Faculty of Pharmaceutical Sciences, Nihon Pharmaceutical University
  • Utsunomiya Iku
    Department of Developmental Education, Showa Pharmaceutical University
  • Horiguchi Yoshie
    Department of Medicinal Chemistry, Showa Pharmaceutical University
  • Taguchi Kyoji
    Department of Medicinal Pharmacology, Showa Pharmaceutical University

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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.

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