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(A full discussion of how serotonin modulates the neural circuitry of behavior and emotion is beyond the scope of this review see, e.g., References 11– 13.) Although the neural circuitry responsible for each of these behavioral processes is still being elucidated, in many cases there is at least one specific brain region or nucleus that is critical for a given behavior. Indeed, it is difficult to find a human behavior that is not regulated by serotonin. The behavioral and neuropsychological processes modulated by serotonin include mood, perception, reward, anger, aggression, appetite, memory, sexuality, and attention, among others. 5-HT, serotonin MAOI, monoamine oxidase inhibitor SSRI, selective serotonin reuptake inhibitor. Not surprisingly, serotonin receptors and transporters are a major focus of CNS drug development, and many current medications modulate serotonin neurotransmission. Indeed, virtually every cell in the brain is close to a serotonergic fiber, and nearly all behaviors as well as many other brain functions are regulated by serotonin. The most caudal raphe innervate the spinal cord, while the more rostral raphe, the dorsal raphe nucleus and the medial raphe nucleus, innervate much of the rest of the CNS by diffuse projections. These serotonin-producing neurons form the largest and most complex efferent system in the human brain. In the central nervous system (CNS), serotonin is almost exclusively produced in neurons originating in the raphe nuclei located in the midline of the brainstem. We also highlight specific settings where new serotonergic drugs may be introduced to medical practice in the future.Ĭentral serotonergic pathways, effects, and drugs. Here we review how serotonin and its cognate receptors regulate the function of multiple human organ systems and disease processes.

In time, these advances may lead to therapies with improved efficacy and side-effect profiles, and will enhance our understanding of a variety of neuropsychiatric and medical disorders. These recent findings also imply that developers of new serotonin receptor subtype-selective drugs will need to consider the roles of a given receptor subtype in the physiology of multiple organ systems. These findings may help explain the diverse side effects of serotonergic drugs-from diabetes and metabolic syndrome to valvular heart disease ( 6, 7). These advances have also shown us that serotonin has critically important functions in many human organ systems outside the CNS, including the regulation of energy balance and food intake, GI and endocrine function, and cardiovascular and pulmonary physiology. Other important advances have included the subsequent development of receptor-specific knockout mice, and the development of receptor subtype-selective drugs. Serotonin and serotonin receptors are important in the regulation of virtually all brain functions, and dysregulation of the serotonergic system has been implicated in the pathogenesis of many psychiatric and neurological disorders ( 3, 4).Ī greater understanding of serotonin function has emerged during the last two decades with the cloning of at least 15 serotonin receptors, which are grouped into seven families based on signaling mechanisms ( 5).

Although serotonin (5-hydroxytryptamine, 5-HT) was discovered 60 years ago ( 1), the study of serotonin and its receptors continues to yield new biological insights of medical relevance in virtually all major organ systems, including the cardiovascular, pulmonary, gastrointestinal (GI), and genitourinary systems as well as the central nervous system (CNS) ( 2).

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