What is a neurotransmitter?
Neurotransmitters are the chemical messengers used for communication between neurons. They are released into the synapse (gap between neurons) by the neuron referred to as the presynaptic neuron and then cause some sort of response (generally excitatory, inhibitory, or modulatory) on the postsynaptic neuron (Hook et al, 2019).
Some traditionally recognized neurotransmitters include serotonin, dopamine, and adrenaline.
However, the scope of what a neurotransmitter is has been expanding to include a broader range of signaling chemicals. Now, substances like Nitric Oxide (NO) and ATP (yes, adenosine triphosphate, the one made in the powerhouse of the cell) are beginning to be included as well.
Now let’s make a tier list…
For the purposes of this list, we will be focusing on some of the more traditional neurotransmitters.
Serotonin
To start off, we’ll go with one that is pretty well known: serotonin. This monoamine is involved in the signaling for a huge variety of systems including regulation of mood, sleep, digestion, and more. It is commonly associated with depression and a common treatment for depression for decades has been SSRIs (Selective Serotonin Reuptake Inhibitors) which essentially stop processes that clear serotonin from the synaptic cleft (Preskron, 1997). So serotonin is pretty cool, pretty popular, and I guess with it being linked to our ability to be well, not depressed, it should be pretty high up.
But to put it in the S tier feels too basic. And recent advances in depression treatments support a new theory of depression involving a different neurotransmitter (more on this coming soon). So I say serotonin gets a solid A.
Acetylcholine
Acetylcholine is one of my personal favorites. It’s most commonly known for being used by pre synaptic neurons at the neuromuscular junction which is where nerve meets muscle. This means the release of acetylcholine is essential for movement. My favorite acetylcholine fact is that botulinum toxin can be used to inhibit its release at these junctions which is actually what botox does (Nigam, 2010). Can’t wrinkle if those muscles can’t move. I’m giving acetylcholine an A!
GABA
Ah, the primary inhibitory neurotransmitter in the central nervous system. Inhibition is so important and honestly quite underrated. Without GABA, there would be too much activity which could lead to a whole host of consequences. Low GABA levels are linked to diseases like epilepsy, motor disorders like stiff person syndrome, and even schizophrenia (Levy & Degnan, 2013). And of course, this inhibition is also crucial for sleep which is a personal favorite activity of mine. So, for the essentialness of inhibition, I think we have our first S tier neurotransmitter.
Epinephrine
I may or may not be wearing my epinephrine (aka adrenaline) necklace as I write this; however, I can not say I am a huge fan of this molecule, at least, not as a neurotransmitter. It’s associated with sympathetic nervous system activity which is the part of our autonomic nervous system that responds unconsciously to stressful situations, often referred to as the fight or flight response (C.C medical). When epinephrine is released in my body, I generally want to get out of whatever situation I am in. I almost want to put this guy in D tier, but I guess the responses in my body due to epinephrine helps me get out of that situation so I’ll cut it some slack and put it in C.
Norepinephrine
Norepinephrine (Noradrenaline) is also involved in that fight or flight response and is generally important for arousal and alertness (Tank, 2015). I’m going to go ahead and put this one near its very chemically similar friend epinephrine in the B row.
Glutamate
Now we have our primary excitatory neurotransmitter (the anti-GABA). Glutamate is essential for learning and is believed to be essential in neuroplasticity (aka our brains ability to change which is very cool). Recently, glutamate has been theorized to have a role in depression and ketamine is being utilized as a way to treat treatment resistant depression (Pal, 2021). The results are very impressive and cause long term positive impacts from small doses. I like learning and I like treating depression, so S tier!
Dopamine
Ok, I admit, I have a favorite. Dopamine is extremely important and one of the key processes it is involved in is motivation (Olguín et al, 2016). Its role in reward makes it an important molecule in guiding our behaviors as the presence of dopamine is associated with pleasurable feelings. It is also involved in movement; Parkinson’s disease, a movement disorder, is actually attributed to a decrease in dopamine production in a region called the substantia nigra.
In my eyes, dopamine is a great example of the complexities of the nervous system because it has involvement in multiple systems and its dysregulation can have a huge range of impacts. Its association with pleasurable feelings displays how in moderate amounts dopamine offers positive feelings but in excess we see how it can become harmful like in the case of addictions. So with that I say, S+ tier!!!
To sum it up…
While creating this list, I thought long and hard about how to compare these neurotransmitters and found myself using the approach of, ‘which one could be removed’. The answer: none of them. Each of these neurotransmitters is involved in multiple systems and some dis-regulation of them can cause widespread consequences. So to completely remove any neurotransmitter would be detrimental. This demonstrates how fine tuned our brains are to function in a way where the production and use of neurotransmitters is precise and modulated. All this to say the rankings of these neurotransmitters was quite arbitrary and are based essentially on just my own opinions, but I hope you learned a little bit about the epic chemicals that allow neurons to communicate along the way!
References
C. medical. (n.d.). Epinephrine (adrenaline): What it is, function, deficiency & side effects. Cleveland Clinic. https://my.clevelandclinic.org/health/articles/22611-epinephrine-adrenaline
Hook, V., Kind, T., Podvin, S., Palazoglu, M., Tran, C., Toneff, T., Samra, S., Lietz, C., & Fiehn, O.. (2019). Metabolomics Analyses of 14 Classical Neurotransmitters by GC-TOF with LC-MS Illustrates Secretion of 9 Cell–Cell Signaling Molecules from Sympathoadrenal Chromaffin Cells in the Presence of Lithium. ACS Chemical Neuroscience, 10(3), 1369–1379. https://doi.org/10.1021/acschemneuro.8b00432
Juárez Olguín H, Calderón Guzmán D, Hernández García E, Barragán Mejía G. The Role of Dopamine and Its Dysfunction as a Consequence of Oxidative Stress. Oxid Med Cell Longev. 2016;2016:9730467. doi: 10.1155/2016/9730467. Epub 2015 Dec 6. PMID: 26770661; PMCID: PMC4684895.
Levy, L. M., & Degnan, A. J.. (2013). GABA-Based Evaluation of Neurologic Conditions: MR Spectroscopy. American Journal of Neuroradiology, 34(2), 259–265. https://doi.org/10.3174/ajnr.a2902
Nigam, P. K., & Nigam, A. (2010). Botulinum toxin. Indian journal of dermatology, 55(1), 8–14. https://doi.org/10.4103/0019-5154.60343
Pal M. M. (2021). Glutamate: The Master Neurotransmitter and Its Implications in Chronic Stress and Mood Disorders. Frontiers in human neuroscience, 15, 722323. https://doi.org/10.3389/fnhum.2021.722323
Preskorn S. H. (1997). Clinically relevant pharmacology of selective serotonin reuptake inhibitors. An overview with emphasis on pharmacokinetics and effects on oxidative drug metabolism. Clinical pharmacokinetics, 32 Suppl 1, 1–21. https://doi.org/10.2165/00003088-199700321-00003
Tank, A. W., & Lee Wong, D. (2015). Peripheral and central effects of circulating catecholamines. Comprehensive Physiology, 5(1), 1–15. https://doi.org/10.1002/cphy.c140007
