With every soul-nourishing walk in the woods, every delicious devouring of a chocolate fudge cake, our brains are bathed in a molecule called dopamine. It’s renowned as one of our main feel-good chemicals. Neurons in our brains release it when we anticipate getting something we desire, like the allure of a romantic night out. In that case, dopamine motivates us to be playful and look our best. And when we’re sharing a laugh in good company, dopamine, alongside its partner oxytocin, drives the feelings of pleasure we experience. These two neurotransmitters are widely regarded as our bodies’ reward-seeking messengers that make life worth living—at least on a neural level.
But dopamine’s intoxicating reputation for setting off those gratifying fireworks in the brain belies how important it is beyond the brain. Along with other neurotransmitters, it has a secret life, moonlighting in various jobs throughout the body in ways unrelated to our conscious feelings or emotions. Researchers are amassing evidence that reveals how these molecular messengers function in disease and how our diet and medicine can shape their delicate balance outside of neurons. So-called “neurotransmitters” have a wealth of hidden talents we’re just beginning to appreciate.
And the influence of neurotransmitters outside our neural neighborhood didn’t start with us. Dating back to ancient microbes, the planet’s first animals, and even plants, these mysterious chemicals orchestrate cellular communication across a diverse swathe of organisms. Scientists have started unravelling how myriad lifeforms have long been harnessing the powers of neurotransmitters—even in the complete absence of any neural circuitry.
How and why do these feel-good chemicals suffuse the tree of life on a molecular level? And what good can brain chemicals be to organisms without brains?
Neurotransmitters wear many hats.
Illustrative answers to these questions exist in the humble sea sponge, one of our most distant and simple animal relatives. Even though it has no neurons, it relies on the activity of neurotransmitters, including ones called GABA and glutamate. In us and other brainy animals, these molecules work like on-and-off switches for neurons—GABA tamps down brain cell chatter, to protect from signal overload, while glutamate encourages cells to communicate. In sea sponges, the opposing actions of these two chemical transmitters cause contractions in a sort of “sneezing” action that dispels build-ups of debris in sponges’ pores.
Curiously, these two neurotransmitters are also manufactured by our muscle cells to make them relax and contract. That’s the same molecules performing similar functions for wildly different organisms—sea sponges and us. Even for evolution, that’s a neat trick.
In these diverse contexts, neurotransmitters are used by cells to communicate, not only between different departments of our own bodies—for example, translating gut activity into mood—but also, with the outside world. Since microbes, animals, and plants release these very same molecules, the cells that make up these different organisms can interpret and react to a world that throws a lot at us.
Even calling these chemical intermediaries “neurotransmitters” may be selling their full range of action a bit short. Russian Academy of Sciences plant biologist Victoria Roshchina recommends ditching the moniker “neurotransmitter” altogether, referring to them instead as “chemical biomediators” to reflect the breadth of their biological roles beyond the nervous system.
Examples of the multifunctionality of neurotransmitters abound in the human body.
Alongside its role in our brain, dopamine lives another life—deep within our waste filtration system. Inside the wound-up, spaghetti-structured tubes of each of our kidneys, cells produce dopamine directly, the amount fluctuating with the varying salt levels in our blood. The chemical crucially keeps our blood pressure in check by directing excess salts and water circulating in the blood into our pee, which carries roughly 60 percent of the salt we excrete.
There is something of a Goldilocks zone for dopamine levels here—patients suffering chronic high blood pressure, or hypertension, typically have either abnormally low or elevated amounts of dopamine in their kidneys, but exactly what causes such irregularities in levels of the neurotransmitter there remains unclear. Scientists recently found that if just one of five kidney-based dopamine receptors starts to malfunction, people tend to become less tolerant to salt and their blood pressure increases.
Dopamine doesn’t stop at balancing salts. In the human pancreas, at the core of our bodies’ blood-sugar regulatory department, dopamine orchestrates, in concert with another neurotransmitter called norepinephrine, the key hormonal actors—insulin, which lowers blood sugar, and glucagon, which raises it. I like to imagine my pancreatic cells rapidly manufacturing their own dopamine to direct glucagon to hold off, and insulin to buffer the monumental sugar load in my morning Nutella.1
Studies in humans and rodents show that levels of dopamine in the blood sharply spike following consumption of a “mixed meal” containing protein and carbs. As reported in a 2019 study, University of Pittsburgh molecular biologist Zachary Freyberg and colleagues found that cells in the pancreas finely tune levels of dopamine production in response to glucose to help regulate insulin’s release and blood-sugar homeostasis.
Even plants make use of neurotransmitters for some quick-fire defenses.
Another major feel-good chemical, serotonin, famed for fueling euphoric sensations, isn’t constrained to the brain either. In the bacterial milieu of the gastrointestinal tract, serotonin plays an outsized role. In fact, the vast majority of our body’s serotonin is produced not in the brain but in the gut, by special cells—called enterochromaffin cells—embedded in the gut’s mucus-coated wall.2 This serotonin is vital for maintaining microbial homeostasis in the gut, which involves directing a variety of our body’s immune response teams, including natural killer cells—a kind of white blood cell that destroys other cells afflicted by pathogens—to combat infections.
Imbalances in gut serotonin levels are often associated with disorders such as inflammatory bowel disease, irritable bowel syndrome, and gluten allergies. But exactly what causes this imbalance isn’t clear. Some of the bacterial residents in our gut microbiome produce metabolites that cause enterochromaffin cells to release more serotonin. Diet might also play a role in adjusting serotonin levels, particularly when we consume foods high in the essential amino acid tryptophan—one of serotonin’s key building blocks.
But serotonin wielding its effect outside the brain can compete with the same chemical inside the brain. For instance, while brain serotonin promotes bone growth, gut serotonin is thought to inhibit it. Neurotransmitters in the brain are independent from those elsewhere since they cannot cross the blood-brain barrier. However, certain medications can cross this barrier, so treatments targeting the brain can also disrupt the balance of neurotransmitters elsewhere. For instance, bromocriptine, a medication for treating Parkinson’s disease and other conditions, once thought to solely function through dopamine-sensitive regions in the brain, has now been shown to directly influence insulin- and glucagon-releasing cells in the pancreas, combating type II diabetes.3, 4
Understanding neurotransmitters’ body-wide roles in disease and dysfunction is also helping advance the development of new medicines that modulate their non-neural signaling. A team of researchers in the United Kingdom published findings in 2023 that showed serotonin in the bloodstream contributing to obesity by tamping down the beneficial burning (thermogenesis) of healthy brown fat, a type of fat that helps regulate your body temperature in cold conditions. Since burning brown fat increases energy expenditure and also improves metabolism, scientists are now exploring medications that lower blood serotonin as a strategy to treat obesity.
Beyond their influence outside of the human nervous system, many of the neurotransmitters that induce happiness and motivation in us are also found in organisms that lack brains altogether. For example, some bacterial species living within the guts of newborn mice produce their own serotonin. A team of researchers led by scientists at Weill Cornell Medicine reported in 2024 that this serotonin helped tune the mouse’s immune system so that the developing rodent’s gut would be amenable to harboring the commensal microbes.
Recent research suggests that bacterial neurotransmitters and animals have been interacting for a long time—some 700 million years. That’s at least 100 million years before nervous systems were even a thing on Earth.5 A 2023 study, for example, provided an exciting glimpse into neurotransmitters’ rich evolutionary history as they mediated cellular crosstalk between single-celled lifeforms and Earth’s earliest and simplest animals. Specifically, the researchers showed that sea sponges have receptors for dopamine-like chemicals despite not being able to produce those chemicals themselves—unlike their life-long bacterial partners, which can.
I like to imagine my pancreatic cells rapidly manufacturing their own dopamine.
One hypothesis proposes that the predecessors of neurotransmitters first evolved as chemicals that produced injury-related signals. This model holds that certain chemicals released during wound-healing responses eventually became signals for coordinating whole-body defense strategies. Serotonin, for example, is thought to have emerged as a chemical byproduct from melatonin biosynthesis, which was likely used by ancient bacteria as an antioxidant, providing protection from the sun and low oxygen levels on the young Earth.
Even plants make use of neurotransmitters for some emergency defenses. Within minutes of an insect nibbling a leaf, Arabidopsis plants can release glutamate, alerting distant leaves to up their defenses.6 Likewise, serotonin is one of the neurotransmitters that stinging nettle plants use, alongside acetylcholine and histamine and others, to irritate human skin with a burning tingle upon contact with its bristly hairs.7
Neurotransmitters are also key for the millimeter-size, pancake-like marine animal Trichoplax adhaerens (roughly translated as “hairy plate”). This species is part of a group called placozoans, some of the simplest creatures alive. They have no nervous system—they’re not much more than a flat aggregation of cells. Yet surprisingly, eating for this strange species is a social occasion. How does it manage to chow with its fellow pancake blobs while staying alert to any danger?
Confronting this puzzle recently, researchers showed how these animals are able to recoil in different directions using adrenaline, the fight-or-flight neurotransmitter. It is responsible for coordinating the collective beating direction of all the microscopic hairs, or cilia, that help it glide like a snail along the seafloor.
So, while “neuro”-transmitters play a headlining role in making human life pleasurable, these formidable chemicals harken back to a far simpler time in the evolution of life. Like an ancient language surviving through generations long-gone, the chemical messengers we call neurotransmitters have served for millions of years as a universal intermediate between living things and the dynamic world that surrounds them.
From the moment you wake up to pee, to the bacterial harmonies at work in your gut, to your next attempt at tackling an unwieldy growth of tingling spring weeds, we’re reminded of an ancient language at work within our bodies that echoes across a wide stretch of evolutionary space and time. 
Lead image: artacet / Shutterstock
References
1. Aslanoglou, D., et al. Dopamine regulates pancreatic glucagon and insulin secretion via adrenergic and dopaminergic receptors. Translational Psychiatry 11, 59 (2021).
2. Banskota, S., Ghia, J.E., & Khan, W.I. Serotonin in the gut: Blessing or a curse. Biochimie 161, 56-64 (2019).
3. Aslanoglou, D., et al. Dual pancreatic adrenergic and dopaminergic signaling as a therapeutic target of bromocriptine. iScience 25, 104771 (2022).
4. Bonifazi, A., et al. Development of novel tools for dissection of central versus peripheral dopamine D2-like receptor signaling in dysglycemia. Diabetes 73, 1411-1425 (2024).
5. Xiang, X., et al. Potential for host-symbiont communication via neurotransmitters and neuromodulators in an aneural animal, the marine sponge Amphimedon queenslandica. Frontiers in Neural Circuits 17, 1250694 (2023).
6. Toyota, M., et al. Glutamate triggers long-distance, calcium-based plant defense signaling. Science 361, 1112-1115 (2018).
7. Roshchina, V.V. Evolutionary considerations of neurotransmitters in microbial, plant, and animal cells. In Lyte, M., Freestone, P. (Eds.) Microbial Endocrinology Springer, New York, NY (2010).
