A Comparison of the Subsecond Dynamics of Neurotransmission of Dopamine and Serotonin

Abstract

The neuromodulators dopamine (DA) and serotonin (5-hydroxytryptamine; 5-HT) are similar in a number of ways. Both monoamines can act by volume transmission at metabotropic receptors to modulate synaptic transmission in brain circuits. Presynaptic regulation of 5-HT and DA is governed by parallel processes, and behaviorally, both exert control over emotional processing. However, differences are also apparent: more than twice as many 5-HT receptor subtypes mediate postsynaptic effects than DA receptors and different presynaptic regulation is also emerging. Monoamines are amenable to real-time electrochemical detection using fast scan cyclic voltammetry (FSCV), which allows resolution of the subsecond dynamics of release and reuptake in response to a single action potential. This approach has greatly enriched understanding of DA transmission and has facilitated an integrated view of how DA mediates behavioral control. However, technical challenges are associated with FSCV measurement of 5-HT and understanding of 5-HT transmission at subsecond resolution has not advanced at the same rate. As a result, how the actions of 5-HT at the level of the synapse translate into behavior is poorly understood. Recent technical advances may aid the study of 5-HT in real-time. It is timely, therefore, to compare and contrast what is currently understood of the subsecond characteristics of transmission for DA and 5-HT. In doing so, a number of areas are highlighted as being worthy of exploration for 5-HT. KEYWORDS: Serotonin, dopamine, comparison, electrochemistry, electrophysiology, fast scan cyclic voltammetry S ince the existence of serotonin (5-HT, 5-hydroxytryptamine) was confirmed in the brain 60 years ago, it has been the subject of intense study. 1 5-HT is implicated in sensory, motor, emotional, and cognitive processing and is thought to be involved to some extent in most psychiatric disorders. 2 The most well-identified functions of 5-HT are its involvement in anxiety, depression, and impulsivity. Accordingly, a detailed knowledge of the pharmacological and cellular effects of antidepressants, anxiolytics, and other psychotropic drugs that target the 5-HT system has emerged. However, how the effects of these drugs translate into raised mood or decreased anxiety is not well understood. Furthermore, how different behavior− brain 5-HT level associations fit together remains unclear. For instance, anxiolysis on reducing brain 5-HT is well established, suggesting that 5-HT increases anxiety. 3,4 However, anxiety is often comorbid with depression which is classically associated with low 5-HT 5−7 (but see ref 8 for a thorough discussion of the conflicting findings regarding 5-HT in depression). Also, SSRIs effectively treat both disorders. Therefore, no unified relationship between 5-HT levels and behavior is yet established. Indeed, the years of research that have come before could indicate that a simple relationship does not exist. However, it is also possible that studies to date have not provided a sufficiently det...

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