IN-VIVO CHRONOAMPEROMETRIC MEASUREMENTS OF THE CLEARANCE OF EXOGENOUSLY APPLIED SEROTONIN IN THE RAT DENTATE GYRUS

The present study evaluated high-speed chronoamperometry as a method f or measuring the clearance of serotonin (5-HT) from extracellular spac e in vivo. Male Sprague-Dawley rats were anaesthetized and a Nafion-co ated, carbon fiber electrode, attached to a multibarrel pipette, was l owered into the subgranular layer of the dentate gyrus, a region which receives dense serotonergic innervation, or the corpus callosum, a fi ber tract relatively devoid of the 5-HT transporter (SERT). Serotonin, pressure ejected into these regions, produced replicable electrochemi cal signals. The amplitude and time course of the signals were signifi cantly prolonged in the corpus callosum compared to the dentate gyrus. Similarly, signals produced by locally applied 5-HT in the dentate gy rus of rats following destruction of hippocampal serotonergic innervat ion with 5,7-dihydroxytryptamine (5,7-DHT), were significantly enhance d compared to those observed in control animals. The time course of th e 5-HT signal was significantly prolonged by local application of the selective 5-HT reuptake inhibitor, fluvoxamine, into the dentate gyrus . By contrast, fluvoxamine did not modify the clearance of 5-HT when l ocally applied into the dentate gyrus of 5,7-DHT lesioned rats or into the corpus callosum of intact rats. Taken together, these data demons trate that in intact rats, the SERT contributes to the clearance of ex ogenously applied 5-HT from the extracellular space. Under the experim ental conditions used in this study, high-speed chronoamperometry prov ed to be a reliable method for directly measuring extracellular 5-HT a nd appears to be a valuable tool for the study of 5-HT clearance by th e SERT in vivo. (C) 1997 Elsevier Science B.V.