Document Detail


Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats.
MedLine Citation:
PMID:  21889317     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and norepinephrine re-uptake and is a promising candidate for the treatment of obesity. Obesity is associated with lower striatal dopamine D2 receptor availability, which may be related to disturbed regulation of food intake. This study assesses the effects of chronic tesofensine treatment on food intake and body weight in association with changes in striatal dopamine D2/D3 receptor (D2/3R) availability of diet-induced obese (DIO) rats. Four groups of 15 DIO rats were randomized to one of the following treatments for 28days: 1. tesofensine (2.0mg/kg), 2. vehicle, 3. vehicle+restricted diet isocaloric to caloric intake of group 1, and 4. tesofensine (2.0mg/kg)+a treatment-free period of 28days. Caloric intake and weight gain decreased significantly more in the tesofensine-treated rats compared to vehicle-treated rats, which confirms previous findings. After treatment discontinuation, caloric intake and body weight gain gradually increased again. Tesofensine-treated rats showed significantly lower D2/3R availability in nucleus accumbens and dorsal striatum than both vehicle-treated rats and vehicle-treated rats on restricted isocaloric diet. No correlations were observed between food intake or body weight and D2/3R availability. Thus, chronic tesofensine treatment leads to decreased food intake and weight gain. However, this appears not to be directly related to the decreased striatal D2/3R availability, which is mainly a pharmacological effect.
Authors:
Elsmarieke van de Giessen; Kora de Bruin; Susanne E la Fleur; Wim van den Brink; Jan Booij
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-8-31
Journal Detail:
Title:  European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology     Volume:  -     ISSN:  1873-7862     ISO Abbreviation:  -     Publication Date:  2011 Aug 
Date Detail:
Created Date:  2011-9-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111390     Medline TA:  Eur Neuropsychopharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2011. Published by Elsevier B.V.
Affiliation:
Department of Nuclear Medicine, Academic Medical Center University of Amsterdam, Amsterdam, The Netherlands.
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