The Rise and Fall of Neurotransmitters

By Neuroskeptic | August 15, 2015 5:46 am

There are dozens of neurotransmitters in the human brain. How do neuroscientists decide which transmitters are most important? Are there trends and fashions in neuroscience, such that some transmitters rise and fall in popularity?

I searched PubMed for nine different neurotransmitters, and downloaded the ‘Results by Year’ data to track the number of peer-reviewed papers published each year from 1960 to 2014. The results are very interesting:

neurotransmitters2

Here are some of my observations in no particular order:

The stagnation of serotonin (red): after growing steadily from 1960 to 2005, the number of papers about serotonin has flat-lined. This is possibly a reflection of the stagnation of research into selective serotonin re-uptake inhibitor (SSRI) antidepressants which likewise plateaued around 2005 (although it has started to grow again lately, unlike serotonin). This, in turn, may be related to the fact that most of the SSRI drugs went off-patent around this period. However, this can’t explain why GABA (purple) and endocannabinoids (black) stagnated over the same period. Hmm.

Dopamine (blue) is on the march: it’s the only transmitter that’s been steadily growing research since 1960.

The decline of noradrenaline/norepinephine (green): it was once the hottest transmitter, but something happened in the mid 1980s, and noradrenaline’s research output flat-lined, and then began to shrink. What went wrong? Maybe it was related to…

The rise and fall of substance p (orange) and the endorphins (pale blue): these two neuropeptides were discovered to be neurotransmitters in the late 1970s. Research on them grew rapidly but it didn’t last – by the early 1990s, they had each entered a decline from which they’ve never recovered. At one point the endorphins were more popular than GABA, but by 2014, 28 times more papers were published about GABA than about endorphins.

Note: This post is an update of one of my first ever posts, from 2008.

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  • https://plus.google.com/u/0/101046916407340625977/posts Rolf Degen

    Glutamate also seems to be in an incessant upward trend, though I don’t know how it fares in comparison. The endocannabinoids were once held dearly as “retrograde messengers”, but that concept did not catch on.

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      Glutamate is a bit difficult because it’s an amino acid as well as a neurotransmitter. Therefore search “glutamate” will get papers about proteins and genetics and nutrition, as well as neurotransmission.

      Which is why I didn’t include it on the graph.

      However if you search “glutamate” AND “brain”, the trend is most similar to the GABA trend (which makes sense): growth until about 2003, then stagnation until 2012, then growth again (the recent growth is actually quite large).

  • Gabriel Castellanos

    Maybe the problem with noradrenaline is that there are almost no drugs specific for this neurotransmitter.. and maybe less association with a single disease…?

  • Daniel San

    Would I be correct in thinking that the trend on endocannabinoids is also a reflection on the political reigns loosening for research in that area?

  • http://jayarava.blogspot.com Jayarava

    The “flatlined” comment needs to be put in context. We are still seeing *4000* articles per year on serotonin. About 11 per day! That is, to my eyes, an astoundingly huge amount of research! No one person could keep up with all the research on serotonin.

    There’s one more line you need to add. Which is “first world GDP”. It looks just like the serotonin line. Although the plateau in research outputs seems to begin a little before the economic crisis, which I cannot explain.

    Behind your observations there seems to be an assumption that research funds are unlimited, that the number of articles could keep on growing with no reference to external factors. I’m sure you’re not really assuming this, but you make no reference at all to the availability of funding in general.

    It seems to me that what needs to be explained, is not stagnation in any research area, because this is what we’d expect given the economic climate, but how dopamine continues to attract growing funding. It’s dopamine that is the odd one out.

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  • benkz1

    dopamine is easily explained due to addiction research if I had to guess

    • http://blogs.discovermagazine.com/neuroskeptic/ Neuroskeptic

      I think it’s a mixture: dopamine is researched in the context of drugs and addiction, but also Parkinson’s disease, and computational / cognitive neuroscience of reward and learning. Maybe the fact that it has a broad “base” is what allows it to grow.

  • CL

    Substance P has an intresting history, with a ton of money spent on developing antagonists, I believe every major pharma have had a couple of NK1 antagonists in their pipelines, and many were brought all the way to phase III where they failed for pain, anxiety, depression and dependence. Still, there is lots of data out there indicating a big role for SP and the NK1 receptor, but the biology is complex with lots of feed-back and feed-forward regulation. Maybe partial agonists is the way to go,,,

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Neuroskeptic is a British neuroscientist who takes a skeptical look at his own field, and beyond. His blog offers a look at the latest developments in neuroscience, psychiatry and psychology through a critical lens.

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