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.