TY - JOUR
T1 - Triple monoamine inhibitor tesofensine decreases food intake, body weight, and striatal dopamine D2/D3 receptor availability in diet-induced obese rats
AU - van de Giessen, Elsmarieke
AU - de Bruin, Kora
AU - la Fleur, Susanne E.
AU - van den Brink, Wim
AU - Booij, Jan
PY - 2012
Y1 - 2012
N2 - The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and norepinephrine reuptake 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. (C) 2011 Elsevier B.V. and ECNP. All rights reserved
AB - The novel triple monoamine inhibitor tesofensine blocks dopamine, serotonin and norepinephrine reuptake 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. (C) 2011 Elsevier B.V. and ECNP. All rights reserved
U2 - https://doi.org/10.1016/j.euroneuro.2011.07.015
DO - https://doi.org/10.1016/j.euroneuro.2011.07.015
M3 - Article
C2 - 21889317
SN - 0924-977X
VL - 22
SP - 290
EP - 299
JO - European neuropsychopharmacology
JF - European neuropsychopharmacology
IS - 4
ER -