Low Dopamine D2 Receptor Increases Vulnerability to Obesity Via Reduced Physical Activity, Not Increased Appetitive Motivation.
The dopamine D2 receptor (D2R) has received much attention in obesity studies. Data indicate that D2R is reduced in obesity and that the TaqA1 D2R variant may be more prevalent among obese persons. It is often suggested that reduced D2R 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 D2R contributes to obesity through alterations in energy expenditure and activity.



We generated a D2R knockdown (KD) mouse line and assessed both energy expenditure and appetitive motivation under conditions of diet-induced obesity.



The 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.



These data suggest the primary contribution of altered D2R signaling to obesity lies in altered energy expenditure rather than the induction of compulsive overeating.
Department of Psychology, Queens College and the Graduate Center, City University of New York, Flushing, New York; Department of Neurobiology (JAB, ST, XZ), Chicago, Illinois. Electronic address: jbeeler@qc.cuny.edu.
Jeff A
JA
Beeler
Interdisciplinary Scientist Training Program, Chicago, Illinois.
Rudolf P
RP
Faust
Department of Neurobiology (JAB, ST, XZ), Chicago, Illinois.
Susie
S
Turkson
Department of Medicine (HY), University of Chicago, Chicago, Illinois.
Honggang
H
Ye
Department of Neurobiology (JAB, ST, XZ), Chicago, Illinois.
Xiaoxi
X
Zhuang
D000818:Animals; D001786:Blood Glucose; D001835:Body Weight; D002153:Calorimetry, Indirect; D002755:Choice Behavior / Q000502:physiology; D003216:Conditioning, Operant / Q000502:physiology; D004195:Disease Models, Animal; D004734:Energy Metabolism / Q000502:physiology; D005247:Feeding Behavior / Q000502:physiology*; D005260:Female; D020022:Genetic Predisposition to Disease; D006799:Housing, Animal; D008297:Male; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009042:Motivation / Q000502:physiology*; D009043:Motor Activity / Q000502:physiology*; D009765:Obesity / Q000378:metabolism* / Q000523:psychology; D017448:Receptors, Dopamine D2 / Q000235:genetics / Q000378:metabolism*
D001786:Blood Glucose; C000600618:DRD2 protein, mouse; D017448:Receptors, Dopamine D2
Behavioral thrift; D(2)R; Dietary induced obesity; Reward deficiency; Running wheels; Voluntary exercise