대뇌피질에서 Methamphetamine의 5-Hydroxytryptamine 유리 기전 = mechanism of methamphetamine-evoked release of 5-Hydroxytryptamine in rat cerebral cortex slices

다국어 초록 (Multilingual Abstract)

Methamphetamine (MAP) is a well known psychostimulant. It has been reported that MAP induces release of various neurotransmitters from brain regions, and is capable of enhancement of cognitive function. Cerebrocortical serotonergic system is involved in memory process. We examined the mechamism of MAP-induced [³H]5-hydroxytryptamine ([³H]5-HT) release in rat hippocampal slices. MAP induced the release of [³H]5-HT in a dose dependent manner (1-300 цM). At 10 цM concentration of MAP, [³H]5-HT was released over 400% of resting period. In the presence of 1 цM yohimbine, MAP-induced [³H]5-HT release potentiated. MAP-induced [³H]5-HT release was not inhibited by 1 цM tetrodotoxin, indicating the action site of MAP is located on the presynaptic terminal. MAP-induced [³H]NE release was not altered by voltage-sensitive calcium channel blockers (nitrendipine, ω-conotoxin GVIA and ω-agatoxin IVA). Fluoxetine (1 цM), a selective 5-HT transporter blocker, significantly inhibited MAP-induced [³H]5-HT release. MAP-induced [³H]5-HT release was inhibited by MK-801 (10 цM), but not by D-AP5 or DNQX. Also, MAP failed to stimulate the release of [³H]aspartate even in 100 цM. MAP-induced release of [³H]NE was reduced by inhibitors of nitric oxide (NO) synthase, 7-nitroindazole (10 цM) and L-NMMA (300 Цm), and potentiated by cGMP phosphodiesterase inhibitor, zaprinast (30 цm). Our results suggest that MAP induces 5-HT release by reversal of transporter which is located in presynaptic terminal, and that NO is involved in this process.