Brain Serotonin Neurotransmission: An Overview and Update With an Emphasis on Serotonin Subsystem Heterogeneity, Multiple Receptors, Interactions With Other Neurotransmitter Systems, and Consequent Implications for Understanding the Actions of Serotone

Knowledge about serotonergic neurotransmission has been expanding rapidly. Recent research hasdelineated 15 molecularly different serotonin receptors and multiple, discrete neuronal and nonneuronal(including endocrine) pathways and mechanisms that mediate the many functions of serotonin.Nonetheless, gaps remain regarding aspects of the anatomy and physiology of serotonin in its roles asa neurotransmitter, a neuromodulator, and a hormone. Few serotonin receptor-selective drugs areavailable for clinical use. A group of selective serotonin reuptake inhibitors (SSRIs) remain the agentswith greatest therapeutic utility, although the mechanisms underlying their delayed efficacy, whichclearly result from adaptive consequences following repeated administration rather than early uptakeinhibition of serotonin by itself, are incompletely understood and appear to involve changes in signaltransduction and gene expression in serotonergic and other neurotransmitter systems.