Carlsson: dopamine is a brain transmitter

The research record

This is the project's file for this landmark, as written and checked. Sources are listed at the end; anything not yet confirmed is marked "Not yet verified".

Who

Arvid Carlsson with Margit Lindqvist, Tor Magnusson and Bengt Waldeck (Lund, Sweden; Carlsson moved to Gothenburg in 1959, per a biographical review). Nobel Prize in Physiology or Medicine 2000, shared with Paul Greengard and Eric Kandel, with Carlsson cited for showing that dopamine is a brain transmitter.

What happened

In 1957 (Nature 180:1200, "3,4-Dihydroxyphenylalanine and 5-hydroxytryptophan as reserpine antagonists"), Carlsson, Lindqvist and Magnusson showed that L-DOPA counteracts the effects of reserpine in animals (rabbits, according to a later review): reserpine-treated animals lose spontaneous movement and L-DOPA restores it. A 1958 Science paper by Carlsson, Lindqvist, Magnusson and Waldeck ("On the presence of 3-hydroxytyramine in brain", 127:471) showed dopamine itself is present in the brain, so it was not just a noradrenaline precursor. That dopamine is enriched in the basal ganglia was reported in 1959 (Hornykiewicz's 2010 history dates it so); this file does not credit that step to the 1958 paper.

Why it moved us toward a cure

It established the dopamine system as the thing that is lost (landmark 1 supplied the Parkinson's link). The ideas behind cell replacement, gene therapy and dopamine-rescue strategies all start here. It also gave the first animal model and the logic for L-DOPA, which treats symptoms only.

Outcome

Advanced. A foundation, but the work is symptomatic and does not modify the disease.

Sources

• Carlsson, Lindqvist & Magnusson, Nature 1957;180:1200, DOI 10.1038/1801200a0, PMID 13483658
• Carlsson, Lindqvist, Magnusson & Waldeck, Science 1958;127(3296):471, DOI 10.1126/science.127.3296.471, PMID 13529006
• Hornykiewicz, "A brief history of levodopa", J Neurol 2010, DOI 10.1007/s00415-010-5741-y (abstract: dopamine shown in brain 1957, enriched in basal ganglia 1959)
• Nobel Prize 2000 press release (laureates and rationale read via search summary)
• Not yet verified: the full text of both papers (neither has an abstract on PubMed); species and doses (rabbits comes from a secondary review); who first measured striatal enrichment in 1959 and in which paper.