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Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
The physiological role of the serotonin transporter on serotonin neuronal membranes apparently is to inactivate serotonin that has been released into the synaptic cleft. Drugs that inhibit the uptake of serotonin increase the amount of serotonin in the synaptic cleft and enhance serotonergic neurotransmission. As an adaptive response to the increased amount of serotonin in the synaptic cleft, serotonin neurons decrease their firing and release of serotonin to limit the magnitude of the increase in extracellular serotonin concentration. The increase in extracellular serotonin in rat brain caused by inhibitors of the serotonin uptake carrier has been characterized by brain microdialysis coupled to liquid chromatography with electrochemical detection. These drugs cause rapid accumulation of extracellular serotonin in several brain regions, although the increase in frontal cortex may be smaller than in other nerve terminal regions or in the cell body-containing raphe region.
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