Sonja K Billes

Neuroscience

Sonja K Billes & Michael A Cowley

A role for dopamine in neuroendocrine regulation of food intake

Obesity is a growing health problem, for which there are few safe

effective treatments.  In a society where palatable high calorie food

is abundant, the rewarding properties of food certainly contribute to

consumption of palatable food beyond the necessary caloric

requirement.  Despite increasing evidence that brain reward systems

play an important role in regulating food intake, little is known

about regulation of hedonic feeding.  Neuroendocrine factors like

leptin are traditionally believed to regulate energy balance through

direct actions on neurons in the medial hypothalamus.  Recent evidence

suggests that these neuroendocrine factors also influence motivation

through direct actions on mesolimbic dopamine neurons, providing a

physiological basis for the already documented regulation of food

intake by dopaminergic drugs.  How these factors affect dopaminergic

signaling and what reward system nuclei are important for mediating

the effects of these neuroendocrine factors on food intake remains to

be determined.  In order to address these questions, we investigated

which dopamine receptor types (D1 or D2) mediate the acute anorectic

effects of leptin.  Through pharmacological blockade or genetic

deletion of the D1 and D2 dopamine receptors, we demonstrate that the

acute hypophagic effects of leptin are partially mediated by D2

dopamine receptors.  We are in the process of extending this study to

examine which dopamine receptor type is important for the hypophagic

effects of a physiologic signal that increases food intake, ghrelin.

Understanding how reward systems affect appetite will not only

increase our understanding of brain physiology, but also allow for the

development of more effective antiobesity drugs.