Bromocriptine/SKF38393 treatment ameliorates obesity and associated metabolic dysfunctions in obese (ob/ob) mice

doi:10.1016/S0024-3205(97)00599-7

Life Sciences

Volume 61, Issue 10, 1 August 1997, Pages 951-956

https://doi.org/10.1016/S0024-3205(97)00599-7 Get rights and content

Abstract

It has been postulated that dopaminergic activities comprise a major functional component of a central regulatory system for metabolism which can be manipulated by dopamine modulating drugs. The present study is aimed at delineating the role and importance of pharmacological dopaminergic activation in the regulation of metabolism during obesity and diabetes. We treated C57BL/6J ob/ob mice for 2 weeks with bromocriptine (dopamine D₂ agonist), SKF38393 (dopamine D₁ agonist), both drugs combined or vehicle and monitored the effects of such treatment on body composition, food consumption, and serum metabolites. Bromocriptine and SKF38393 individually produced moderate improvements in obesity, hyperglycemia, and hyperinsulinemia. However, a combination of bromocriptine plus SKF38393 resulted in major reductions in body weight (7.5g), body fat (40%), food consumption (42%), and serum concentrations of glucose (59%), triglyceride (37%), free fatty acid (45%) and insulin (49%) while increasing protein mass (8%). These results indicate that regulatory components of metabolism in the ob/ob mouse are modulated by and/or are comprised of dopaminergic activities. Importantly, dopaminergic $D_{1} D_{2}$ receptor coactivation maximizes this dopaminergic response (i.e., improvement of metabolic abnormalities) in these mice.

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TE might, however, induce an indirect, long-term effect on DA D2 RA due to enhancing amounts of synaptic DA by blockade of DAT. Both D1 and D2 agonists have been shown to reduce food intake in animal models of obesity (Cincotta et al., 1997; Scislowski et al., 1999; Davis et al., 2009). Further, apparently there occur functional synergistic interactions between D1 and D2 receptor systems in the basal ganglia, which play a critical role in neuronal output, and thus behavioural effects (Walters et al., 1987; Waddington, 1989).
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Bromocriptine/SKF38393 treatment ameliorates obesity and associated metabolic dysfunctions in obese (ob/ob) mice

Abstract

Metabolism

Life Sciences

Metabolism

Metabolism

Brain Research

Int. J. Obesity

Am. J. Physiol.

Ann. Nutr. Metab.

Diabetes Care