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The mesolimbic dopamine system is the primary neural circuit mediating motivation, reinforcement, and reward-related behavior. The activity of this system and multiple behaviors controlled by it are affected by changes in feeding and body weight, such as fasting, food restriction, or the development of obesity. Multiple different peptides and hormones that have been implicated in the control of feeding and body weight interact with the mesolimbic dopamine system to regulate many different dopamine-dependent, reward-related behaviors. In this review, we summarize the effects of a selected set of feeding-related peptides and hormones acting within the ventral tegmental area and nucleus accumbens to alter feeding, as well as food, drug, and social reward.

Obesity is a significant problem, and increased food intake is thought to underlie much of the increase in obesity levels. Recently, there has been much discussion and debate about the role of the individual macronutrients, carbohydrates, fat, and protein, in the rise in obesity levels and its associated comorbidities, but overall there has been little study of how different treatments and stimuli that affect feeding impact the intake of individual macronutrients. In these studies, we tested whether two treatments leading to altered feeding, acute cocaine injection and an acute fast, differentially affect the intake of individual macronutrients using a three diet choice paradigm. Cocaine strongly inhibited the intake of each individual test diet (carbohydrate, fat, and protein), but there were no differences between its effects on the intakes of each individual diet. In contrast, an acute fast had little effect on the intake of any of the diets and did not differentially affect the intake of the three test diets. Thus, these studies demonstrate that cocaine can effectively inhibit the intake of feeding independent of its macronutrient content, and significantly advance our understanding of the neural regulation of individual macronutrient intake.