DB 3 – The role of 5-HT receptors in depression
Many psychiatric medications modulate serotonin (5-HT). 5-HT receptors can be grouped into 7 types; 5-HT1-5HT7 with each type having subtypes. Identify the types and subtypes that have the most relevance to depression treatment and discuss the role of each relevant subtype.
Post needs 3 resources including one for these – the others can be up to you
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DB 3 – The Role of 5-HT Receptors in Depression
Depression continues to be a burden in modern society. Health care organizations have recommended antidepressants such as selective serotonin inhibitors (SSRIs) as the prescribed drugs to curb depression. Major depressive disorder (MDD) is still the most common lifelong disorder, accounting for more lost productivity than any other illness. The 5-HT receptor is known for regulating aggressive and impulsive behavior and modulating depression. It is worth mentioning that activation of the 5-HT 1B receptor lowers serotonin levels in the brain through effects on release, synthesis, and reuptake. This study discusses the seven types of receptors (5-HT1-5HT7) and their subtypes that have the most significance to depression treatment and the role of each relevant subtype.
The 5-HT1 receptors help neuromodulation by decreasing blood pressure and heart rate by inducing peripheral vasodilation. 5-HT1A is one of the 5-HT1 subtypes that provides the brain with an auto-inhibitory feedback loop that regulates serotonin neurotransmission. Besides, the 5-HT1B receptor subtype function as heteroreceptors and controls the release of other neurotransmitters such as glutamate and acetylcholine (Pithadia & Jain, 2009). Also, the 5-HT1D as a receptor subtype inhibits adenylate cyclase. On the other hand, 5-HT2 binds the endogenous neurotransmitter serotonin and stimulates contraction of the lower oesophageal sphincter. The subtypes, including 5-HT2A, 5-HT2B, 5-HT2C, helps as a messenger for phospholipase C activation. They play the role of neuron excitation, stomach fundus contraction, and modulation of CSF volume and transferrin production, respectively. The 5-HT2 receptor helps in reducing blood pressure by reducing peripheral resistance and causing vasodilation.
Furthermore, the 5-HT3 receptors help in reducing alcohol intake among humans and animals. They help lower visceral pain reflex and reduce pain related to duodenal distension. Dyspepsia patients would thus benefit from the increased visceral sensitivity. Also, the 5-HT3 M is a messenger for the ligand ion channel and stimulates vomiting by vagal neuron excitation. It also enables the nociceptive nerve ending that leads to pain. On the other hand, the 5-HT4 receptors play a critical role in increasing the colonic motor activity and the increased Ach release, which accelerate gastrointestinal transit. Also, it increases intestinal motility and helps treat gastroesophageal flux, irritable bowel syndrome, and constipation.
The 5-HT5 receptors are G-protein-coupled receptors (GPCRs) preferentially couple to Gs and enhance cAMP production (Yohns & Samuels, 2017). However, there has been limited information concerning the significant roles of this receptor. The primary subtypes include 5-HT5A and 5-HT5B receptors, and both have no selective agonist and antagonist available. The 5-HT6 receptor participates in activating the adenylate cyclase and in the modulation of CNS Ach release. It also helps in improving learning, cognition, and memory. There are no subtypes for 5-HT6. Also, the 5-HT7 receptor helps activate adenylate cyclase and helps in smooth muscle relaxation. They are highly expressed in the thalamic nuclei and the limbic regions. It consists of three subtypes; 5-HT7A, 5-HT7B, and 5-HT7D (Quintero-Villegas & Valdes-Ferrer, 2020). The recognized role of the 5-HT7 receptor includes circadian rhythm, thermoregulation, sleep, learning, and memory. Scientists continue to discover the different 5-HT receptor subtypes. They monitor the precise involvement of receptor subtypes in various pathological states and physiological processes. 5-HT receptor modifying medications have now demonstrated their therapeutic relevance in multiple diseases, including emesis, anxiety, migraine, and other neurologic and periphery ailments.
Pithadia, A. B., & Jain, S. M. (2009). 5-Hydroxytryptamine receptor subtypes and their modulators with therapeutic potentials. Journal of clinical medicine research, 1(2), 72.Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3318857/#:~:text=5%2Dhydroxytryptamine%20(5%2DHT,5%2DHT7%20have%20been%20identified.
Quintero-Villegas, A., & Valdés-Ferrer, S. I. (2020). Role of 5-HT 7 receptors in the immune system in health and disease. Molecular Medicine, 26(1), 1-8. Retrieved from https://molmed.biomedcentral.com/articles/10.1186/s10020-019-0126-x
Yohn, C. N., Gergues, M. M., & Samuels, B. A. (2017). The role of 5-HT receptors in depression. Molecular brain, 10(1), 1-12. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483313/