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

Lisa M. Davis, Michael Michaelides, Lawrence J. Cheskin, Timothy H. Moran, Susan Aja, Paul A. Watkins, Zhengtong Pei, Carlo Contoreggi, Karen McCullough, Bruce Hope, Gene Jack Wang, Nora D. Volkow, Panayotis K. Thanos

Research output: Contribution to journalArticlepeer-review

Abstract

Background: The dopamine (DA) D2 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)152-162
Number of pages11
JournalNeuroendocrinology
Volume89
Issue number2
DOIs
StatePublished - Feb 2009

Keywords

  • Bromocriptine
  • Dopamine
  • Dopamine Dreceptor
  • Dopamine transporter
  • Leptin

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

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