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Comparative study of fluoxetine, sibutramine, sertraline, and dexfenfluramine on the morphology of serotonergic nerve terminals using serotonin immunohistochemistry.

Authors
Kalia-M; O'Callaghan-JP; Miller-DB
Source
Brain Res 2000 Mar; 858(1):92-105
NIOSHTIC No.
20020714
Abstract
We compared the effects of treatment with high doses of fluoxetine, sibutramine, sertraline, and dexfenfluramine for 4 days on brain serotonergic nerve terminals in rats. Methylenedioxymethamphetamine (MDMA) and 5,7-dihydroxytryptamine (5,7-DHT) were used as positive controls because both compounds deplete brain serotonin. Food intake and body weight changes were also monitored and yoked, pair-fed animals were used to control for possible changes in morphology due to nutritional deficits. Fluoxetine, sibutramine, sertraline and dexfenfluramine all produced a significant reduction in body weight. Fluoxetine, sibutramine and sertraline treatment resulted in no depletion of brain serotonin but produced morphological abnormalities in the serotonergic immunoreactive nerve network. In contrast, dexfenfluramine and MDMA depleted brain serotonin and produced morphological changes in the serotonin nerve network. These results indicate that even though fluoxetine, sibutramine and sertraline do not deplete brain serotonin, they do produce morphological changes in several brain regions (as identified by serotonin immunohistochemistry). Dexfenfluramine and MDMA, on the other hand, markedly deplete brain serotonin and also produce morphological changes. Collectively, these results lend support to the concept that all compounds acting on brain serotonin systems, whether capable of producing serotonin depletion or not, could produce similar effects on the morphology of cerebral serotonin systems.
Keywords
Morphology; Nerves; Neurotoxicity; Laboratory-animals; Animals; Animal-studies; Brain-disorders; Brain-function
Contact
Department of Biochemistry, Molecular Pharmacology and Anesthesiology, Jefferson Medical College, Thomas Jefferson University, 233 South 10th Street, Suite 309, Philadelphia, PA 19107, USA
CODEN
BRREAP
Publication Date
20000306
Document Type
Journal Article
Email Address
mkalia@msn.com
Fiscal Year
2000
NTIS Accession No.
NTIS Price
Issue of Publication
1
ISSN
0006-8993
NIOSH Division
HELD
Source Name
Brain Research
State
WV; PA
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