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Abstract:
Evidence from pharmacological, neuroimaging, postmortem, and genetic studies underlines the various roles of 5-HT receptor subtypes in the pathogenesis of major depressive disorder. Recent investigations further supported the notion of their interaction with the antidepressant medication and advanced the knowledge on underlying mechanisms of their action. The heterogeneous properties of individual 5-HT receptors offer a chance for development of new generation of antidepressants, which may be more beneficial and effective than traditional selective serotonin reuptake inhibitors (SSRIs). Antagonists of 5-HT2A, 5-HT2C, 5-HT3, 5-HT6, and 5-HT7 receptors, as well as agonists of 5-HT1A, 5-HT1B, 5-HT2C, 5-HT4, and 5-HT6 receptors, were observed to produce antidepressant-like responses. Paradoxical antidepressant-like effects of both agonists and antagonists of 5-HT receptors are likely connected to the diverse neurochemical mechanisms they instantiate. Augmented behavioral effects of SSRIs and other antidepressants used in combined treatment with 5-HT receptor agonists or antagonists have also been reported. The involvement of 5-HT receptors in depression is complex. Identifying the role of 5-HT receptors in response to antidepressants is an essential step in recognizing their mechanisms of action and, thereby, potentially producing more effective antidepressants with fewer side effects in patients with major depressive disorder.
