The sun on your skin, a shared laugh, or savouring a delicious meal—these experiences often evoke a sense of well-being.  At the heart of these feelings lies a remarkable neurotransmitter: serotonin.

Often dubbed the "feel-good" chemical, serotonin (5-hydroxytryptamine, or 5-HT) is far more than a simple mood booster. It's a neurotransmitter and hormone that orchestrates a symphony of functions, influencing mood regulation, sleep cycles, appetite, digestion, and even cardiovascular health. The key to understanding serotonin's versatility lies in the intricate network of its receptors.

Serotonin receptors

Serotonin exerts its effects by binding to specific receptors on cell surfaces. These receptors are proteins that receive chemical signals and trigger responses within the cell. Serotonin receptors are categorised into seven distinct classes, known as 5-HT1 to 5-HT7, each with various subtypes.

The majority of serotonin receptors belong to the G protein-coupled receptor (GPCR) superfamily, a vast group of receptors involved in a myriad of physiological processes. When serotonin binds to a GPCR, it initiates a chain reaction within the cell, modulating various signalling pathways, including ion channels, phospholipase C, and adenylyl cyclase. This intricate interplay allows serotonin to fine-tune its influence, ensuring precise control over diverse bodily functions.

Serotonin's wide-reaching influence

Serotonin receptors are distributed throughout the brain and body, playing pivotal roles in an astonishing array of behaviours and physiological processes. In fact, it's challenging to pinpoint a human behaviour that isn't influenced by serotonin to some degree.

For instance, the 5-HT2C receptor has been implicated  in regulating food intake and body weight, influencing everything from reward processing and movement to appetite and energy balance. Whereas 5-HT7 has been shown to be crucial for maintaining regular sleep patterns and circadian rhythms, our body's internal clock. This highlights serotonin's crucial role in maintaining overall health and well-being.

Serotonin and mental well-being

The connection between serotonin and mental health is undeniable, yet complex.  While low serotonin levels have been implicated in depression and anxiety, the relationship is not as simple as "more serotonin equals happier." Selective Serotonin Reuptake Inhibitors (SSRIs), a common class of antidepressants, boost serotonin levels in the brain by blocking its reabsorption into neurons. However, the exact mechanism by which SSRIs alleviate symptoms remains a topic of ongoing research.

Case study: Aripiprazole

One example of how our understanding of serotonin receptors has translated into clinical applications is the drug aripiprazole. This atypical antipsychotic, used to treat conditions like schizophrenia and bipolar disorder, interacts with both dopamine and serotonin receptors.

Unlike many other antipsychotics that solely block dopamine receptors, aripiprazole acts as both an activator and a blocker of specific serotonin receptors. This means it activates the receptor, but to a lesser degree than serotonin itself, offering a more balanced approach to mood regulation. Additionally, aripiprazole acts as an antagonist at the 5-HT2A receptor, blocking excessive serotonin activity that can contribute to hallucinations and delusions.

Conclusion

Serotonin is a multifaceted neurotransmitter that plays a crucial role in regulating mood, sleep, appetite, and digestion. Its receptors, spread throughout the brain and body, mediate a wide range of physiological and behavioural processes. Understanding serotonin and its receptors is essential for developing effective treatments for various psychiatric conditions. Aripiprazole’s unique action on serotonin receptors exemplifies the therapeutic potential of targeting these pathways.

Continued research into the structure, function, and pharmacology of serotonin receptors is crucial for the development of novel therapeutics for a wide range of disorders. Advances in our understanding of serotonergic neurotransmission hold the promise of improved treatments for mental illness, neurodegenerative diseases, and other conditions with significant unmet medical needs.

Further Reading

For more detailed information, consider reading:

• Berger, Miles et al. “The expanded biology of serotonin.” Annual Review of Medicine vol. 60 (2009): 355-66. doi:10.1146/annurev.med.60.042307.110802
• Celada, Pau et al. “The therapeutic role of 5-HT1A and 5-HT2A receptors in depression.” Journal of psychiatry & neuroscience : JPN vol. 29,4 (2004): 252-65.
• He, Y., Cai, X., Liu, H. et al. “5-HT recruits distinct neurocircuits to inhibit hunger-driven and non-hunger-driven feeding.” Mol Psychiatry 26, 7211–7224 (2021). https://doi.org/10.1038/s41380-021-01220-z
• Parajulee, Apeksha, and Kuglae Kim. “Structural studies of serotonin receptor family.” BMB reports vol. 56,10 (2023): 527-536. doi:10.5483/BMBRep.2023-0147
• Monti JM, Jantos H. “The role of serotonin 5-HT7 receptor in regulating sleep and wakefulness.” Rev Neurosci. (2014) doi:10.1515/revneuro-2014-0016.

About the artwork

Myrzagalym Amina, a 10-year-old student from NIS Taraz, Kazakhstan, created an artwork depicting the serotonin receptor due to its crucial role in mental health and mood regulation. She was fascinated by its structure and influence on various biological processes like aggression, anxiety, cognition, and sleep. Throughout the project, Amina enhanced her knowledge of proteins and applied advanced sketching techniques, such as impasto, glazing, and sgraffito, to add depth and texture to her work, where she highlights the important role of serotonin receptors in the brain.

View the artwork in the virtual 2023 PDB Art exhibition.

Written by: Paulyna Magaña