In vivo chronoamperometric recordings were used to determine if the majority of serotonin transporters (SERTs) in the dorsal raphe nucleus (DRN) are functionally active. This was achieved by comparing the clearance of exogenously applied serotonin (5-HT) from the extracellular fluid (ECF) of the DRN to that in the CA3 region of the hippocampus, an area with lower SERT density. Serotonin was pressure ejected into these regions in anesthetized rats and reproducible electrochemical signals measured by carbon fiber microelectrodes were recorded. Consistent with SERT density as measured by [3H]cyanoimipramine binding in these brain regions (DRN≫CA3), clearance of 5-HT was significantly faster in DRN compared to that in the CA3 region. The selective serotonin reuptake inhibitor, fluvoxamine, prolonged 5-HT clearance in both CA3 and DRN. It is known that the norepinephrine transporter (NET) contributes to clearance of 5-HT in the dentate gyrus (DG) but not in CA3. Given that the DRN receives noradrenergic innervation, it was also determined if the NET contributes to 5-HT clearance in the DRN. Destruction of the NET with the neurotoxin 6-hydroxydopamine failed to alter 5-HT clearance parameters in the DRN. These data support the hypothesis that serotonin transporters are functionally active in the DRN, that serotonin clearance is mediated primarily by the SERT in the DRN and that the faster clearance of 5-HT from this region is related to its greater density of functional SERTs.
|Number of pages||9|
|State||Published - Nov 15 2002|
Bibliographical noteFunding Information:
This research was supported by U.S. Public Health Service grants MH57001 (A.F.), MH01245 (G.A.G.), THECB-ARP #3659-0034-1999 (L.C.D.) and the Veterans Administration. The authors wish to thank Dr. Saloua Benmansour and Dr. Julie Hensler for critical reading of the manuscript.
- Dorsal raphe nucleus
- Serotonin transporter
ASJC Scopus subject areas
- Neuroscience (all)
- Molecular Biology
- Clinical Neurology
- Developmental Biology