title: Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats.
abstract: 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 28 days: 1. tesofensine (2.0 mg/kg), 2. vehicle, 3. vehicle+restricted diet isocaloric to caloric intake of group 1, and 4. tesofensine (2.0 mg/kg)+ a treatment-free period of 28 days. 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: Department of Nuclear Medicine, Academic Medical Center University of Amsterdam, Amsterdam, The Netherlands. e.m.vandegiessen@amc.uva.nl
authors: Elsmarieke
authors: E
authors: van de Giessen
authors: Kora
authors: K
authors: de Bruin
authors: Susanne E
authors: SE
authors: la Fleur
authors: Wim
authors: W
authors: van den Brink
authors: Jan
authors: J
authors: Booij
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology* / Q000627:therapeutic use; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects*; D002149:Energy Intake / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D014179:Neurotransmitter Uptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D011869:Radioligand Assay / Q000379:methods / Q000706:statistics & numerical data; D051381:Rats; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D050637:Receptors, Dopamine D3 / Q000378:metabolism*
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; D014179:Neurotransmitter Uptake Inhibitors; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; C518479:Tesofensine