Serotonin receptors in depression: from A to B

Abstract

The role of serotonin in major depressive disorder (MDD) is the focus of accumulating clinical and preclinical research. The results of these studies reflect the complexity of serotonin signaling through many receptors, in a large number of brain regions, and throughout the lifespan. The role of the serotonin transporter in MDD has been highlighted in gene by environment association studies as well as its role as a critical player in the mechanism of the most effective antidepressant treatments - selective serotonin reuptake inhibitors. While the majority of the 15 known receptors for serotonin have been implicated in depression or depressive-like behavior, the serotonin 1A (5-HT _1A) and 1B (5-HT _1B) receptors are among the most studied. Human brain imaging and genetic studies point to the involvement of 5-HT _1A and 5-HT _1B receptors in MDD and the response to antidepressant treatment. In rodents, the availability of tissue-specific and inducible knockout mouse lines has made possible the identification of the involvement of 5-HT _1A and 5-HT _1B receptors throughout development and in a cell-type specific manner. This, and other preclinical pharmacology work, shows that autoreceptor and heteroreceptor populations of these receptors have divergent roles in modulating depression-related behavior as well as responses to antidepressants and also have different functions during early postnatal development compared to during adulthood.

Keywords: 5-HT1A; 5-HT1B; 5-HTT; MDD; antidepressant; major depressive disorder; selective serotonin reuptake inhibitors; serotonin; serotonin receptor.

Figure 1.. Schematic illustrating the inhibitory effects of serotonin (5-hydroxytryptamine, 5-HT) 1A (5-HT _1A) (red) and 5-HT _1B (blue) receptors on the normal firing and neurotransmitter release of a neuron (top).

Activation of 5-HT _1A receptors results in decreased firing (middle), while activation of 5-HT _1B receptors causes decreased neurotransmitter release through actions in the presynaptic terminal (bottom).

Figure 2.. Diagram summarizing the roles of autoreceptor and heteroreceptor populations of serotonin (5-hydroxytryptamine, 5-HT) 1A (5-HT _1A) and 5-HT _1B receptors on behavior during development and adulthood.

5-HTT, serotonin transporter.