Low Dopamine D 2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation

• Published in: Biological psychiatry (1969) Vol. 79; no. 11; pp. 887 - 897
• Main Authors: Beeler, Jeff A, Faust, Rudolf P, Turkson, Susie, Ye, Honggang, Zhuang, Xiaoxi
• Format: Journal Article
• Language: English
• Published: 01.06.2016
• Subjects: Psychiatric/Mental Health; Voluntary exercise; D 2R; Dietary induced obesity; Reward deficiency; Behavioral thrift; Running wheels
• ISSN: 0006-3223
• DOI: 10.1016/j.biopsych.2015.07.009

AbstractBackgroundThe dopamine D 2 receptor (D 2R) has received much attention in obesity studies. Data indicate that D 2R is reduced in obesity and that the TaqA1 D 2R variant may be more prevalent among obese persons. It is often suggested that reduced D 2R generates a reward deficiency and altered appetitive motivation that induces compulsive eating and contributes to obesity. Although dopamine is known to regulate physical activity, it is often neglected in these studies, leaving open the question of whether reduced D 2R contributes to obesity through alterations in energy expenditure and activity. MethodsWe generated a D 2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity. ResultsThe KD mice did not gain more weight or show increased appetitive motivation compared with wild-type mice in a standard environment; however, in an enriched environment with voluntary exercise opportunities, KD mice exhibited dramatically lower activity and became more obese than wild-type mice, obtaining no protective benefit from exercise opportunities. ConclusionsThese data suggest the primary contribution of altered D 2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating.