Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action
Vesicular transport regulates monoamine storage and release but is not essential for amphetamine action
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DOI：
10.1016/s0896-6273(00)80418-3
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发表时间：
1997-12-01
期刊：
影响因子：
16.2
通讯作者：
Edwards, RH
中科院分区：
文献类型：
--
作者：
Fon, EA;Pothos, EN;Edwards, RH
为了评估胞吐释放在单胺信号传导中的作用，我们破坏了神经元囊泡单胺转运蛋白2（VMAT 2）基因。VMAT 2（-/-）小鼠很少移动，喂养不良，并在出生后几天内死亡。单胺细胞群和它们的投射与野生型同窝出生的小鼠没有区别，但突变小鼠的大脑显示单胺急剧减少。使用突变动物的中脑培养物，安非他明而不是去极化诱导多巴胺释放。在体内，安非他明增加运动，促进进食，并延长VMAT 2（-/-）动物的生存，表明精确的，时间调节的单胺胞吐释放是不需要某些复杂的行为。此外，VMAT 2杂合子的大脑含有比野生型同窝仔低得多的单胺水平，并且去极化诱导杂合子比野生型培养物释放更少的多巴胺，这表明VMAT 2表达调节单胺的储存和释放。
To assess the role of exocytotic release in signaling by monoamines, we have disrupted the neuronal vesicular monoamine transporter 2 (VMAT2) gene. VMAT2(-/-) mice move little, feed poorly, and die within a few days after birth. Monoamine cell groups and their projections are indistinguishable from those of wild-type littermates, but the brains of mutant mice show a drastic reduction in monoamines. Using midbrain cultures from the mutant animals, amphetamine but not depolarization induces dopamine release. In vivo, amphetamine increases movement, promotes feeding, and prolongs the survival of VMAT2(-/-) animals, indicating that precise, temporally regulated exocytotic release of monoamine is not required for certain complex behaviors. In addition, the brains of VMAT2 heterozygotes contain substantially lower monoamine levels than those of wild-type littermates, and depolarization induces less dopamine release from heterozygous than from wild-type cultures, suggesting that VMAT2 expression regulates monoamine storage and release.