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 serotonergic drugs.

Knowledge about serotonergic neurotransmission has been expanding rapidly. Recent research has delineated 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 as a neurotransmitter, a neuromodulator, and a hormone. Few serotonin receptor-selective drugs are available for clinical use. A group of selective serotonin reuptake inhibitors (SSRIs) remain the agents with greatest therapeutic utility, although the mechanisms underlying their delayed efficacy, which clearly result from adaptive consequences following repeated administration rather than early uptake inhibition of serotonin by itself, are incompletely understood and appear to involve changes in signal transduction and gene expression in serotonergic and other neurotransmitter systems.