Abstract
The effects of dexfenfluramine on the release of brain dopamine and serotonin into striatal dialysates were measured in freely moving rats. Samples collected every 20 min were assayed for dopamine and serotonin by high-performance liquid chromatography in a single run. The administration of a lower anorectic dose of dexfenfluramine (0.5 or 1.0 mg/kg intraperitoneally) significantly increased dialysate serotonin concentrations without affecting those of dopamine. A higher dexfenfluramine dose (2.5 mg/kg intraperitoneally) increased both serotonin and dopamine. The increase in dopamine could be blocked by administering the mixed-acting serotonin antagonist methiothepin (20 μM), and was reproduced by applying serotonin (3–10 μM) directly to striatal neurons. Tetrodotoxin (1 μM) added to the striatal perfusates decreased the basal release of dopamine and serotonin; it also blocked the effect of dexfenfluramine (2.5 mg/kg intraperitoneally) on dopamine release and decreased the increment in serotonin release (by ≈70%). Amphetamine (1 mg/kg subcutaneously) or phentermine (2 mg/kg intraperitoneally) increased dialysate dopamine concentrations without affecting those of serotonin, and tetrodotoxin (1 μM) failed to block the response to amphetamine. These findings suggest that (1) lower anorectic doses of dexfenfluramine release serotonin but not dopamine, and (2) higher doses of dexfenfluramine also increase dopamine release by an indirect mechanism mediatedvia serotonin.
Footnotes
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Send reprint requests to: Dr. R. J. Wurtman, Massachusetts Institute of Technology E25–604, Department of Brain and Cognitive Sciences, 77 Massachusetts Avenue, Cambridge, MA 02139. E-mail: dick{at}mit.edu
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↵1 This work was supported by the Center for Brain Sciences and Metabolism Charitable Trust.
- Abbreviations:
- d-fen
- dexfenfluramine
- DA
- dopamine
- 5-HT
- serotonin
- TTX
- tetrodotoxin
- 5-HTP
- 5-hydroxytryptophan
- L-DOPA
- l-dihydroxyphenyl acetic acid
- SDS
- sodium dodecyl sulfate
- NaH2PO4
- sodium dihydrogen phosphate
- aCSF
- artificial cerebrospinal fluid
- ANOVA
- analysis of variance
- Received January 31, 1997.
- Accepted November 17, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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