Melanocortin 3 Receptor Signaling in Midbrain Dopamine Neurons Increases the Motivation for Food Reward.

The central melanocortin (MC) system mediates its effects on food intake via MC3 (MC3R) and MC4 receptors (MC4R). Although the role of MC4R in meal size determination, satiation, food preference, and motivation is well established, the involvement of MC3R in the modulation of food intake has been less explored. Here, we investigated the role of MC3R on the incentive motivation for food, which is a crucial component of feeding behavior.

Inhibitory Effect of the Melanocortin Receptor Agonist Melanotan-II (MTII) on Feeding Depends on Dietary Fat Content and not Obesity in Rats on Free-Choice Diets.

Introduction: Conflicting data exist on sensitivity changes of the melanocortin system during diet-induced obesity. We hypothesized that melanocortin sensitivity depends on diet composition, in particular on the fat content rather than the level of obesity. The aim of this study was to determine the influence of diet composition on feeding responses to a melanocortin receptor agonist, using free-choice diets that differ in food components.

Central melanocortins regulate the motivation for sucrose reward.

The role of the melanocortin (MC) system in feeding behavior is well established. Food intake is potently suppressed by central infusion of the MC 3/4 receptor agonist α-melanocyte stimulating hormone (α-MSH), whereas the MC 3/4 receptor inverse-agonist Agouti Related Peptide (AGRP) has the opposite effect. MC receptors are widely expressed in both hypothalamic and extra-hypothalamic brain regions, including nuclei involved in food reward and motivation, such as the nucleus accumbens (NAc) and the ventral tegmental area.

Cannabinoid, melanocortin and opioid receptor expression on DRD1 and DRD2 subpopulations in rat striatum.

The striatum harbors two neuronal populations that enable action selection. One population represents the striatonigral pathway, expresses the dopamine receptor D1 (DRD1) and promotes the execution of motor programs, while the other population represents the striatopallidal pathway, expresses the dopamine receptor D2 (DRD2) and suppresses voluntary activity. The two populations integrate distinct sensorimotor, cognitive, and emotional information streams and their combined activity enables the selection of adaptive behaviors.

AAV-mediated gene transfer of the obesity-associated gene Etv5 in rat midbrain does not affect energy balance or motivated behavior.

Several genome-wide association studies have implicated the transcription factor E-twenty- six version 5 (Etv5) in the regulation of body mass index. Further substantiating the role of Etv5 in feeding behavior are the findings that targeted disruption of Etv5 in mice leads to decreased body weight gain and that expression of Etv5 is decreased in the ventral tegmental area and substantia nigra pars compacta (VTA/SNpc) after food restriction. As Etv5 has been suggested to influence dopaminergic neurotransmission by driving the expression of genes that are responsible for the synthesis and release of dopamine, we investigated if expression levels of Etv5 are dependent on nutritional state and subsequently influence the expression levels of tyrosine hydroxylase.

Nutritional state affects the expression of the obesity-associated genes Etv5, Faim2, Fto, and Negr1.

Obesity is a risk factor for type II diabetes, atherosclerosis, and some forms of cancer. Variation in common measures of obesity (e.g.

An overview on how components of the melanocortin system respond to different high energy diets.

High energy diets are used to model the obesity epidemic. Moreover, from a variety of genetic studies, it has become clear that the melanocortin system plays an important role in the regulation of energy metabolism. Since most dietary interventions are not standardized, fat/sugar-induced effects on the melanocortin system vary distinctly among different studies.