IN-VIVO CHRONOAMPEROMETRIC MEASURES OF EXTRACELLULAR SEROTONIN CLEARANCE IN RAT DORSAL HIPPOCAMPUS - CONTRIBUTION OF SEROTONIN AND NOREPINEPHRINE TRANSPORTERS

The effects of blockade of serotonin (5-HT) and norepinephrine (NE) tr ansporters (SERT and NET, respectively) on the removal of locally appl ied 5-HT from extracellular fluid (ECF) were examined using in vivo ch ronoamperometry. Male Sprague-Dawley rats were anesthetized with chlor atose/urethane, and a Nafion-coated, carbon fiber electrode attached t o a multibarrel micropipette was positioned into either the dentate gy rus or CA3 region of the dorsal hippocampus. Pressure ejection of 5-HT elicited reproducible electrochemical signals of similar peak amplitu de and time course in both structures. Local application of the select ive serotonin reuptake inhibitors (SSRI) fluvoxamine and citalopram pr olonged the clearance of 5-HT in both brain regions and also increased signal amplitude in the CA3 region. These effects were abolished in r ats pretreated with 5,7-dihydroxytryptamine (5,7-DHT), a selective 5-H T neurotoxin. The NE uptake inhibitors desipramine (DMI) and protripty line did not alter the 5-HT signal in the CA3 region but prolonged the clearance of 5-HT in the dentate gyrus; this effect was absent in rat s pretreated with 6-hydroxydopamine (6-OHDA), a selective catecholamin e neurotoxin. The prolongation of the removal of 5-HT from the ECF in the dentate gyrus caused by fluvoxamine or desipramine was of comparab le magnitude and was dose dependent. Furthermore, per picomole of 5-HT applied, the signal amplitude and clearance time were significantly i ncreased in the dentate gyrus of rats lesioned with either 5,7-DHT or 6-OHDA. Only 5,7-DHT treatment caused this effect in the CA3 region. F rom these data, it is inferred that in certain regions of brain (denta te gyrus), both the SERT and NET contribute to the active clearance of exogenously applied 5-HT.