NIDA Intramural Research Program, Baltimore, MD 21224, USA.
NIDA Intramural Research Program, Baltimore, MD 21224, USA.
Curr Biol. 2022 Aug 8;32(15):R817-R824. doi: 10.1016/j.cub.2022.06.060.
Dopamine was first described by George Barger, James Ewens, and Henry Dale in 1910 as an epinephrine-like monoamine compound. Initially believed to be a mere precursor of norepinephrine, it was mostly ignored for the next four decades (Figure 1A). However, in the 1950s Kathleen Montagu showed that dopamine occurred in the brain by itself, and a series of studies by Arvid Carlsson and collaborators demonstrated that dopamine is a bona fide neurotransmitter, a finding that would earn Carlsson the 2000 Nobel Prize in Physiology and Medicine. In a landmark experiment, he pharmacologically blocked all dopamine neurotransmission in rabbits, which rendered them completely paralyzed, and then fully recovered their behavior with an injection of the dopamine precursor L-DOPA, demonstrating that dopamine was essential for self-initiated movement (Figure 1B). A similar effect was quickly reproduced by Oleg Hornykiewicz and collaborators in human Parkinsonian patients. Within a few years, dopamine jumped from relative obscurity to being critical for life as we know it.
多巴胺最初是由 George Barger、James Ewens 和 Henry Dale 在 1910 年描述为一种类似肾上腺素的单胺化合物。最初被认为只是去甲肾上腺素的前体，在接下来的四十年里它基本上被忽视了（图 1A）。然而，在 20 世纪 50 年代，Kathleen Montagu 证明了多巴胺本身存在于大脑中，随后 Arvid Carlsson 及其合作者进行了一系列研究，证明多巴胺是一种真正的神经递质，这一发现使 Carlsson获得了 2000 年诺贝尔生理学或医学奖。在一项具有里程碑意义的实验中，他用药理学方法阻断了兔子体内所有的多巴胺神经传递，使它们完全瘫痪，然后用多巴胺前体 L-DOPA 注射完全恢复了它们的行为，证明了多巴胺对自主运动至关重要（图 1B）。Oleg Hornykiewicz 和他的合作者在人类帕金森病患者中很快复制了类似的效果。在短短几年内，多巴胺从相对默默无闻一跃成为我们所知道的生命的关键。
