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

Vol. 89, No. 2, 2009

Article (Fulltext) Article (PDF 370 KB)

Appetite and Energy Balance

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^a, Michael Michaelides^{b, f, h}, Lawrence J. Cheskin^a, Timothy H. Moran^c, Susan Aja^c, Paul A. Watkins^d, Zhengtong Pei^d, Carlo Contoreggi^e, Karen McCullough^e, Bruce Hope^e, Gene Jack Wang^b, Nora D. Volkow^{b, h}, Panayotis K. Thanos^{b, f–h}

^aDepartment of International Health, Center for Human Nutrition, Johns Hopkins Bloomberg School of Public Health,
^bBehavioral Neuropharmacology and Neuroimaging Laboratory, Department of Medicine, Brookhaven National Laboratory,
^cDepartment of Psychiatry and Behavioral Sciences,Johns Hopkins School of Medicine,
^dKennedy Krieger Institute, Johns Hopkins University School of Medicine, and
^eNational Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, Baltimore, Md., and
^fDepartment of Psychology and
^gNeuroscience Program, SUNY Stony Brook, Stony Brook, N.Y.,
^hLaboratory of Neuroimaging, NIAAA, NIH, Department of Health and Human Services, Bethesda, Md., USA

Address of Corresponding Author

Neuroendocrinology 2009;89:152-162 (DOI: 10.1159/000170586)

Key Words

Bromocriptine
Dopamine
Dopamine D₂receptor
Dopamine transporter
Leptin

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.

Author Contacts

Panayotis K. Thanos
Behavioral Neuropharmacology and Neuroimaging Laboratory
Department of Medicine, Brookhaven National Laboratory
Building 490, Upton, NY 11973 (USA)
Tel. +1 631 344 7056, Fax +1 631 344 5311, E-Mail thanos@bnl.gov

Article Information

Received: January 25, 2008
Accepted after revision: July 2, 2008
Published online: November 4, 2008
Number of Print Pages : 11
Number of Figures : 4, Number of Tables : 4, Number of References : 65

Cited in Web of Science®

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