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If you’re going to biohack your brian, it’s best to understand how and why. This is more difficult than it sounds, as neuroscience and neuropharmacology are ever-changing fields. They are often misunderstood even by researchers themselves.  Don’t get me wrong; I feel there are many scientists contributing greatly to premier research.  The problem lies in debunking theories after they’ve become established norms. We’ve all heard about the serotonin and depression theory [1]; there is much more involved in depression than just serotonin. Conclusion: It’s important to be discerning in your search for knowledge. Everyone has overheard the sentiment, “dopamine is the learning neurotransmitter”- but why? Many would agree, the brain uses any given neurotransmitter for a myriad of processes. Each of these processes makes up who we are, how we react, and what we are capable of.  If this is true, how can we infallibly conclude dopamine is the end-all be-all responsible for learning? Analyzing receptors, and their subtypes, gives us greater insight into the mechanism of action behind learning.

Serotonin has 15 known subtypes [1]. Ranging from excitatory to inhibitory, serotonin receptors wear many hats.  Gastrointestinal motility, neurotransmission, and cardiovascular activity are just some of their responsibilities [2]. Serotonin affects your sleep, sensory experience, locomotion, body temperature, appetite, sex drive, and endocrine system [2]. The 5-HT2A receptor subtype is implicated in cognition just as much as other more popular ones.  5-HT2A agonists, which share their mechanism with some psychedelics, “enhance associated learning” [3].

The accompanying study quantifies conditioning in rats following administration of an 5-HT2A agonist. The results implicate this receptor subtype as a mediator of cognition [3].  Furthermore, inverse 5-HT2A agonists worsened learning [3]. Dysfunction and variations of activity, at the 5-HT2A receptor, are associated with poor cognition as seen in schizophrenic patients [3]. Bacopa, a serotonergic nootropic, has proven its ability to augment memory recall and retention [4]. In conclusion, the 5-HT2A receptor and 5-HT affect our intelligence.

Acetylcholine dysfunction is often implicated in the progression of Alzheimer’s disease.  The conditions enabling Alzheimer’s vary greatly depending on the body of evidence available to you. Some are of the notion it’s insulin resistance. Others believe it is due to buildup of amyloid plaque. Regardless of causative speculation, neurotransmitters are reduced in every Alzheimer’s model [4]. A reduction in acetylcholine is by far the most drastic and apparent [4].  Dementia is associated with a large drop in cholinergic neurotransmission as well [5]. Moving forward, acetylcholine receptors can be categorized as muscarinic and nicotinic (mAChR and nAChR) [5]. Nicotine is known to augment learning by possessing an affinity for nAChR receptors [6]. The important details of nicotine’s mechanism of action have been unknown for some time. Recently, researchers discovered nicotine modulates the communication of other neurotransmitters such as GABA [6]. Nicotine thus strengthens communication in other parts of the brain. Known as “spike-timing-dependent potentiation”, nicotine modulates communication outside of the cholinergic system [6]. The cholinergic system is not only implicated in human cognition, it strengthens transmission between other neurons.  This is just one additional piece of the puzzle. There are many more.

Of all neurotransmitters, dopamine may seem to be a weaker candidate. Have you ever driven yourself to complete a task? Have you then experienced the feeling of reward upon its completion? That is what dopamine feels like [7]. Dopamine directly influences the desire to learn by raising or lowering a feeling of reward [7]. Dopamine is involved in motivation, arousal, locomotion, sex drive, and mood [7]. Does that sound familiar? We know serotonin plays a pivotal role in sexual health, locomotion, and mood. Acetylcholine plays a critical role in movement just like dopamine. The brain does not rely on one neurotransmitter to perform any single function. Augmenting the brain requires a multifaceted approach. Since we’re passionate about nootropics, it may involve a series of trials and errors with a focus on established science. Always give your body the ability to augment itself. Provide vitamins, minerals, and a balanced diet. Make sure you’re well rested, and free of excess stress. Don’t forget to exercise. Finally, remember the brain responds differently to changes in homeostasis. Introducing a nootropic which works for you does not guarantee it will work for your friend. Remember serotonin and GABA play an equal role in learning as acetylcholine and dopamine. Do you lack motivation? Your dopaminergic system may be downregulated. Take the time to understand where you fit in the nootropic spectrum; none of us are alike.

References

[1] M. University, “Serotonin and Other Molecules Involved in Depression,” [Online]. Available: http://thebrain.mcgill.ca/flash/i/i_08/i_08_m/i_08_m_dep/i_08_m_dep.html. [Accessed 7 1 2019].


[2] S. N. Upadhyay, “Serotonin Receptors, Agonists and Antagonists,” 2003. [Online]. Available: http://medind.nic.in/iaw/t03/i1/iawt03i1p1.pdf. [Accessed 7 1 2019].


[3] J. A. Harvey, “Harvey, J. A. (2003). Role of the serotonin 5-HT2A receptor in learning. Learning & Memory, 10(5), 355-362.,” 2003. [Online]. Available: http://learnmem.cshlp.org/content/10/5/355.full%C2%A0%C2%A0. [Accessed 7 1 2019].


[4] Examine, “Bacopa monnieri,” 9 11 2018. [Online]. Available: https://examine.com/supplements/bacopa-monnieri/. [Accessed 8 1 2019].


[5] K. Potter, “Alzheimer’s Disease: Sorting Through Tangles and Clearing up the Plaque,” 4 11 2007. [Online]. Available: http://www.scq.ubc.ca/alzheimers-disease-sorting-through-tangles-and-clearing-up-the-plaque/. [Accessed 8 1 2019].


[6] V. Oikonen, “Cholinergic system,” 12 1 2018. [Online]. Available: http://www.turkupetcentre.net/petanalysis/target_cholinergic_system.html. [Accessed 8 1 2019].


[7] E. Doonan, “Mechanism of nicotine’s learning effects explored,” Cell Press, 4 4 2007. [Online]. Available: https://www.eurekalert.org/pub_releases/2007-04/cp-mon033007.php. [Accessed 8 1 2019].


[8] N. News, “The Role of Dopamine in Motivation and Learning,” 24 11 2015. [Online]. Available: https://neurosciencenews.com/dopamine-learning-reward-3157/. [Accessed 8 1 2019].