Bromocriptine administration reduces hyperphagia and adiposity and differentially affects dopamine D2 receptor and transporter binding in leptin-receptor-deficient Zucker rats and rats with diet-induced obesity.
BACKGROUND
The dopamine (DA) D(2) receptor (D2R) agonist bromocriptine (BC) decreases body fat in animal and human models and increases lean muscle mass, improves glucose intolerance and insulin resistance, and reduces triglycerides and free fatty acids. We have previously shown a negative correlation between D2R and body weight in obese individuals and in rodents, and that chronic food restriction increases D2R binding in genetically obese rats. The purpose of this study was to assess whether the antiobesity and metabolic effects of BC are related to changes in midbrain DA and D2R activity by measuring D2R and DA transporter (DAT) binding in a genetic (leptin-receptor-deficient) and environmental (diet-induced) rodent obesity model.


METHODS
Obese (fa/fa) (leptin-receptor-deficient), lean (FA/FA) Zucker rats and rats with diet-induced obesity (DIO) were treated with 10 mg/kg BC for 4 weeks. Body weight, food intake, locomotor activity and blood glucose levels were measured along with D2R- and DAT-binding levels using in vitro receptor autoradiography.


RESULTS
BC decreased food intake and body fat and increased locomotor activity in both the (fa/fa) and DIO rats. Furthermore, BC increased D2R binding in (fa/fa) but not in DIO rats. Finally, BC increased DAT binding in DIO rats but not in the (fa/fa) rats.


CONCLUSIONS
These observations are all consistent with the existence of unique leptin-DA interactions and the hypothesis that there is hyposensitivity of the DA system in obesity.
Davis
Lisa M
LM
Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
Michaelides
Michael
M
Cheskin
Lawrence J
LJ
Moran
Timothy H
TH
Aja
Susan
S
Watkins
Paul A
PA
Pei
Zhengtong
Z
Contoreggi
Carlo
C
McCullough
Karen
K
Hope
Bruce
B
Wang
Gene Jack
GJ
Volkow
Nora D
ND
Thanos
Panayotis K
PK
D050154:Adiposity / Q000187:drug effects*; D000818:Animals; D001971:Bromocriptine / Q000494:pharmacology*; D004032:Diet / Q000009:adverse effects*; D018491:Dopamine Agonists / Q000494:pharmacology*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000187:drug effects* / Q000378:metabolism*; D004435:Eating / Q000187:drug effects; D006963:Hyperphagia / Q000188:drug therapy*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009765:Obesity / Q000139:chemically induced / Q000188:drug therapy*; D051381:Rats; D011924:Rats, Zucker / Q000235:genetics / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000819:agonists* / Q000378:metabolism*; D054411:Receptors, Leptin / Q000235:genetics / Q000378:metabolism
D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D054411:Receptors, Leptin; D001971:Bromocriptine