Genetic approaches for understanding the role of serotonin receptors in mood and behavior

Serotonin (5-hydroxytryptamine; 5-HT) is an ancient signaling molecule that has a conserved role in modulating mood and behavior. Integral to its pleiotropic actions is the existence of multiple receptors, expressed in distinct but often overlapping patterns within the brain and the periphery. The existence of ∼14 mammalian receptor subtypes, many of which possess similar pharmacological profiles, has made assigning functional roles for these receptors challenging. This challenge has been further compounded by the revelation that a single receptor can have several different functions depending upon where and when it is expressed and activated, that is, in brain versus periphery, or at different developmental time points. This review highlights the contribution of genetic techniques to dissect the specific function of distinct serotonin receptor populations across the life course, with an emphasis on the contribution of different serotonin 1A receptor populations to mood and behavior. Similar approaches hold the promise to elucidate the functional roles of other receptors, as well as the interaction of serotonin with other neuroendocrine modulators of mood and behavior.