Sustained exposure to 3,4-methylenedioxymethamphetamine induces the augmentation of exocytotic serotonin release in rat organotypic raphe slice cultures.
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 Ca(2+)-dependent exocytotic serotonin release is mediated through activation of AMPA receptors and responsible for the sustained MDMA-induced augmentation of serotonin release.
Nagayasu
Kazuki
K
Department of Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan.
Kitaichi
Maiko
M
Shirakawa
Hisashi
H
Nakagawa
Takayuki
T
Kaneko
Shuji
S
D000818:Animals; D002118:Calcium / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D009924:Organ Culture Techniques; D011903:Raphe Nuclei / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000502:physiology; D012701:Serotonin / Q000378:metabolism*; D050486:Serotonin Plasma Membrane Transport Proteins / Q000502:physiology; D013268:Stimulation, Chemical
D018091:Receptors, AMPA; D050486:Serotonin Plasma Membrane Transport Proteins; D012701:Serotonin; D018817:N-Methyl-3,4-methylenedioxyamphetamine; D002118:Calcium