Dopamine and serotonin (5-hydroxytryptamine or 5-HT) are neurotransmitters that are implicated in many psychological disorders. Although dopamine transmission in the brain has been studied extensively in vivo with fast scan cyclic voltammetry, detection of 5-HT using in vivo voltammetric methods has only recently been established. In this work we use two carbon-fiber microelectrodes to simultaneously measure dopamine release in the nucleus accumbens and 5-HT release in the substantia nigra pars reticulata, using a common stimulation in a single rat. We find that 5-HT release is profoundly restricted in comparison with dopamine release despite comparable tissue content levels. Using physiological and pharmacological analysis, we find that 5-HT transmission is mostly sensitive to uptake and metabolic degradation mechanisms. In contrast, dopamine transmission is constrained by synthesis and repackaging. Finally, we show that disruption of serotonergic regulatory mechanisms by simultaneous inhibition of uptake and metabolic degradation can have severe physiological consequences that mimic serotonin syndrome.electrical stimulation | monoamine oxidase inhibitor | selective serotonin reuptake inhibitor D opamine and serotonin (5-hydroxytryptamine or 5-HT) are neurotransmitters with important, conserved roles in the vertebrate nervous system. Dopamine is important in neuronal circuitry that controls reward and in brain regions that regulate movement (1). Assigning a specific functional role to 5-HT has proven more difficult because electrophysiological recordings of 5-HT neurons reveal unchanged firing in response to most stimuli (2). Competing roles have been suggested for dopamine and 5-HT in reward circuitry, with dopamine signals predicting positive stimuli and 5-HT signals predicting negative consequences (3, 4). Biochemically, their regulation is quite similar, with similar proteins regulating synthesis, storage, release, uptake, and metabolism. To compare functional dopamine and 5-HT regulation in the brain, methods have been developed to monitor dynamic changes in their concentrations in the extracellular space.Transient fluctuations of dopamine concentrations in the extracellular space of the nucleus accumbens core (NAc) can be evoked by electrical stimulation of the medial forebrain bundle (MFB) and have been characterized in the rat using in vivo voltammetric methods (5, 6). Dopamine is easily oxidized, and electrochemical methods such as fast-scan cyclic voltammetry can be used for detection (7). A carbon-fiber microelectrode is placed in the brain region of interest. The shape of the cyclic voltammogram identifies dopamine, and its amplitude can be used to calculate concentration. Each cyclic voltammogram can be collected in less than 10 ms, enabling fast, repetitive acquisition. Successive recordings of fluctuations in dopamine concentration lead to visualization of dopaminergic transmission events with subsecond temporal resolution. This method has shown that electrical stimulations of dopaminergic axons ...
Carbon fiber microelectrodes provide the ideal platform for performing ultrafast, selective measurements of electroactive brain molecules. This article highlights the current status of the use of carbon fiber microelectrodes in neurochemical measurements, outlining the most cutting edge findings and technological advances in amperometry and fast-scan cyclic voltammetry.
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