title: 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.
abstract: 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.
authors.affiliation: Department of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Davis
authors.forename: Michael
authors.initials: M
authors.lastname: Michaelides
authors.forename: Lawrence J
authors.initials: LJ
authors.lastname: Cheskin
authors.forename: Timothy H
authors.initials: TH
authors.lastname: Moran
authors.forename: Susan
authors.initials: S
authors.lastname: Aja
authors.forename: Paul A
authors.initials: PA
authors.lastname: Watkins
authors.forename: Zhengtong
authors.initials: Z
authors.lastname: Pei
authors.forename: Carlo
authors.initials: C
authors.lastname: Contoreggi
authors.forename: Karen
authors.initials: K
authors.lastname: McCullough
authors.forename: Bruce
authors.initials: B
authors.lastname: Hope
authors.forename: Gene Jack
authors.initials: GJ
authors.lastname: Wang
authors.forename: Nora D
authors.initials: ND
authors.lastname: Volkow
authors.forename: Panayotis K
authors.initials: PK
authors.lastname: Thanos
mesh_terms: 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
chemical_list: D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; D054411:Receptors, Leptin; D001971:Bromocriptine