Mesolimbic dopamine in obesity and diabetes.

Monoaminergic neurotransmitter dopamine plays a critical role in various vital functions including hormonal regulation, reward, emotions and food intake. Multiple aspects of food intake that include food selection, satiety and energy expenditure could be modulated by changes in central dopaminergic transmission (1,2). Several lines of research indicate that abnormal dopaminergic neurotransmission could be involved in pathophysiological processes leading to obesity. Most of these studies are focused on the hypothalamic dopamine transmission that is believed to play a pivotal role in the guidance of fuel flux and energy homeostasis (3). Generally, these investigations have indicated a decreased dopaminergic signaling in obese subjects (3). For example, dopamine D2 receptors were found to be lower in several brain regions in both obese experimental animals and humans and it has been observed that dopamine D2 agonist bromocriptine can exert favorable metabolic changes in seasonal obesity (3). In line with this contention, obesity is one of the best known side-effect of antipsychotic drugs that exert their actions mostly via antagonism of D2 dopamine receptors (4). It should be noted, however, that there is also evidence indicating that in brain mesolimbic structures responsible for motivation, reward and emotions, particularly in the nucleus accumbens, a situation may be completely different and obesity can be accompanied with an increased dopamine signaling that could determine an increased motivation for food consumption (5). It has become increasingly clear that food shares the ability of many drugs of abuse to activate common reward circuits such Page 1 of 7 Articles in PresS. Am J Physiol Regul Integr Comp Physiol (June 27, 2007). doi:10.1152/ajpregu.00450.2007