Many psychiatric medications modulate serotonin (5-HT)
Serotonin Receptors and their Relevance in Treatment of Depression
For more than a half-century, serotonin (5-hydroxytryptamine; 5-HT) has been implicated in the pathophysiology and treatment of depression (Amidfar et al., 2019). Serotonin-related antidepressants are stipulated to work by acting on serotonin receptors in the central nervous system (CNS). There are different types and subtypes of serotonin receptors. The numbering of serotonin receptors ranges from 5-HT1 to 5-HT7. Subtypes are identified by appending an alphabetical letter to the end of the receptor type (Nautiyal & Hen, 2017). This paper will only cover the receptor types and subtypes relevant to depression treatment.
Postsynaptic 5-HT1A receptors are crucial in treating depression (Nautiyal & Hen, 2017). These receptors are abundant in the CNS, particularly in the septum, hippocampus, amygdala, raphe nucleus, and cerebral cortex. They play a significant role in the inhibition of neuronal discharge. Serotonin reuptake inhibitors act on 5-HT1A in the hippocampus, preventing serotonin reuptake and thus increasing serotonin levels, producing an antidepressant effect in adults (Nautiyal & Hen, 2017).
According to Nautiyal and Hen (2017), the second class of receptors that are heavily involved in treating depression is postsynaptic 5-HT2A. These receptors are concentrated in the prefrontal cortex (Amidfar et al., 2019). The antidepressant effect of selective serotonin reuptake inhibitors (SSRIs) is produced by blocking these receptors in the neocortex.
Furthermore, their blockade affects the prefrontal–subcortical circuits, resulting in beneficial effects when additional 5-HT2A receptor antagonists are prescribed to patients who are resistant to SSRI treatment (Nautiyal & Hen, 2017). Other serotonin receptors, such as 5-HT3, 5-HT6, and 5-HT7, when blocked, augment the serotonin increase elicited by SERT inhibitors like paroxetine (Nautiyal & Hen, 2017).
The density and location of serotonin receptors influence their actions when activated. The majority of the effects of antidepressants are mediated by CNS receptors. The 5-HT1A and 5-HT2A receptors have been extensively studied and are implicated in the treatment of depression. These antidepressants exert their effects by increasing serotonergic activity in neurons by inhibiting serotonin reuptake.
Amidfar, M., Colic, L., Walter, M., & Kim, Y.-K. (2019). Biomarkers of major depression related to serotonin receptors. Current Psychiatry Reviews, 14(4), 239–244. https://doi.org/10.2174/1573400514666181016115747
Nautiyal, K. M., & Hen, R. (2017). Serotonin receptors in depression: from A to B. F1000Research, 6, 123. https://doi.org/10.12688/f1000research.9736.1