Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
14
|
pubmed:dateCreated |
1998-7-27
|
pubmed:abstractText |
Fenfluramine, a serotonin releaser and uptake inhibitor, has been widely prescribed as an appetite suppressant. Despite its popular clinical use, however, the precise neural pathways and specific 5-HT receptors that account for its anorectic effect have yet to be elucidated. To test the hypothesis that stimulation of 5-HT1B receptors is required for the anorectic effect of fenfluramine, we assessed food intake in wild-type and 5-HT1B knock-out mice. Next, to determine possible brain structures and pathways that may contribute to the 5-HT1B-mediated effects of fenfluramine, we studied by immunohistochemistry the induction of the immediate early gene c-fos. Although the effect of fenfluramine on locomotion was indistinguishable between both wild-type and 5-HT1B knock-out mice, the anorectic effect of the drug was absent in only the knock-out mice. Furthermore, the induction of c-Fos immunoreactivity found in the paraventricular nucleus of the hypothalamus (PVN) of wild-type mice was substantially reduced in the knock-outs. Induction in the central amygdaloid nucleus (CeA) and in the bed nucleus of the stria terminalis (BNST), although robust in wild-type animals, was completely absent in knock-out animals. The mixed 5-HT1A/1B agonist RU24969 was able to mimic both the hypophagia and c-fos induction elicited by fenfluramine in wild-type mice, but not in the 5-HT1B knock-out mice. Our results thus demonstrate that stimulation of 5-HT1B receptors is required for fenfluramine-induced anorexia and suggest a role for the PVN, CeA, and BNST in mediating this effect.
|
pubmed:grant | |
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Appetite Depressants,
http://linkedlifedata.com/resource/pubmed/chemical/Fenfluramine,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-fos,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Serotonin,
http://linkedlifedata.com/resource/pubmed/chemical/Serotonin Uptake Inhibitors
|
pubmed:status |
MEDLINE
|
pubmed:month |
Jul
|
pubmed:issn |
0270-6474
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
15
|
pubmed:volume |
18
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
5537-44
|
pubmed:dateRevised |
2007-11-14
|
pubmed:meshHeading |
pubmed-meshheading:9651234-Amygdala,
pubmed-meshheading:9651234-Animals,
pubmed-meshheading:9651234-Anorexia,
pubmed-meshheading:9651234-Appetite Depressants,
pubmed-meshheading:9651234-Body Weight,
pubmed-meshheading:9651234-Drug Evaluation, Preclinical,
pubmed-meshheading:9651234-Feeding Behavior,
pubmed-meshheading:9651234-Fenfluramine,
pubmed-meshheading:9651234-Hypothalamus,
pubmed-meshheading:9651234-Limbic System,
pubmed-meshheading:9651234-Mice,
pubmed-meshheading:9651234-Mice, Knockout,
pubmed-meshheading:9651234-Nerve Tissue Proteins,
pubmed-meshheading:9651234-Proto-Oncogene Proteins c-fos,
pubmed-meshheading:9651234-Receptors, Serotonin,
pubmed-meshheading:9651234-Serotonin Uptake Inhibitors
|
pubmed:year |
1998
|
pubmed:articleTitle |
Absence of fenfluramine-induced anorexia and reduced c-Fos induction in the hypothalamus and central amygdaloid complex of serotonin 1B receptor knock-out mice.
|
pubmed:affiliation |
Center for Neurobiology and Behavior, Columbia University, New York, New York 10032, USA.
|
pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|