Sustained Exposure to 3,4-Methylenedioxymethamphetamine Induces the Augmentation of Exocytotic Serotonin Release in Rat Organotypic Raphe Slice Cultures

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  • Nagayasu Kazuki
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Kitaichi Maiko
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Shirakawa Hisashi
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Nakagawa Takayuki
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan
  • Kaneko Shuji
    Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Japan

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Abstract

3,4-Methylenedioxymethamphetamine (MDMA) causes serotonin efflux via serotonin transporter. Recently, we have reported that sustained exposure to MDMA induced an augmentation of serotonin release in rat raphe serotonergic slice cultures. Here we investigated the mechanism of augmented serotonin release from the slice cultures. Sustained MDMA exposure had no effect on MDMA-induced serotonin efflux in the synaptosomal fraction, whereas either tetrodotoxin, calcium channel inhibitors, or AMPA-receptor antagonists significantly attenuated the augmented serotonin release. These results suggest that the increase in Ca2+-dependent exocytotic serotonin release is mediated through activation of AMPA receptors and responsible for the sustained MDMA-induced augmentation of serotonin release.

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