Abstract
The effects of blockade of serotonin (5-HT) and norepinephrine (NE) transporters (SERT and NET, respectively) on the removal of locally applied 5-HT from extracellular fluid (ECF) were examined usingin vivo chronoamperometry. Male Sprague-Dawley rats were anesthetized with chloralose/urethane, and a Nafion-coated, carbon fiber electrode attached to a multibarrel micropipette was positioned into either the dentate gyrus or CA3 region of the dorsal hippocampus. Pressure ejection of 5-HT elicited reproducible electrochemical signals of similar peak amplitude and time course in both structures. Local application of the selective serotonin reuptake inhibitors (SSRI) fluvoxamine and citalopram prolonged the clearance of 5-HT in both brain regions and also increased signal amplitude in the CA3 region. These effects were abolished in rats pretreated with 5,7-dihydroxytryptamine (5,7-DHT), a selective 5-HT neurotoxin. The NE uptake inhibitors desipramine (DMI) and protriptyline 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 rats pretreated with 6-hydroxydopamine (6-OHDA), a selective catecholamine neurotoxin. The prolongation of the removal of 5-HT from the ECF in the dentate gyrus caused by fluvoxamine or desipramine was of comparable magnitude and was dose dependent. Furthermore, per picomole of 5-HT applied, the signal amplitude and clearance time were significantly increased 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. From these data, it is inferred that in certain regions of brain (dentate gyrus), both the SERT and NET contribute to the active clearance of exogenously applied 5-HT.
Footnotes
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Send reprint requests to: Dr. Lynette C. Daws, Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio TX 78284-7764. E-mail:daws{at}uthscsa.edu
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↵1 This work was supported by United States Public Health Service Grants NS09199, MH29094 and AG06434, National Science Foundation Grant BIR913392, the Veterans Administration and Pharmacia and Upjohn.
- Abbreviations:
- DMI
- desipramine
- 5
- 7-DHT, 5,7-dihydroxytryptamine
- ECF
- extracellular fluid
- Fluvox
- fluvoxamine
- HPLC
- high-performance liquid chromatography
- 5-HIAA
- 5-hydroxyindoleacetic acid
- 5-HT
- 5-hydroxytryptamine (serotonin)
- i.c.v.
- intracerebroventricularly
- i.p.
- intraperitoneally
- NE
- norepinephrine
- NET
- norepinephrine transporter
- PBS
- phosphate-buffered saline
- 6-OHDA
- 6-hydroxydopamine
- SERT
- serotonin transporter
- SSRI
- selective serotonin reuptake inhibitor
- Received December 16, 1997.
- Accepted April 20, 1998.
- The American Society for Pharmacology and Experimental Therapeutics
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