Role of the striatal dopamine, GABA and opioid systems in mediating feeding and fat intake.

Food intake, which is a highly reinforcing behavior, provides nutrients required for survival in all animals. However, when fat and sugar consumption goes beyond the daily needs, it can favor obesity. The prevalence and severity of this health problem has been increasing with time. Besides covering nutrient and energy needs, food and in particular its highly palatable components, such as fats, also induce feelings of joy and pleasure. Experimental evidence supports a role of the striatal complex and of the mesolimbic dopamine system in both feeding and food-related reward processing, with the nucleus accumbens as a key target for reward or reinforcing-associated signaling during food intake behavior. In this review, we provide insights concerning the impact of feeding, including fat intake, on different types of receptors and neurotransmitters present in the striatal complex. Reciprocally, we also cover the evidence for a modulation of palatable food intake by different neurochemical systems in the striatal complex and in particular the nucleus accumbens, with a focus on dopamine, GABA and the opioid system.

Midbrain and Lateral Nucleus Accumbens Dopamine Depletion Affects Free-choice High-fat high-sugar Diet Preference in Male Rats.

Dopamine influences food intake behavior. Reciprocally, food intake, especially of palatable dietary items, can modulate dopamine-related brain circuitries. Among these reciprocal impacts, it has been observed that an increased intake of dietary fat results in blunted dopamine signaling and, to compensate this lowered dopamine function, caloric intake may subsequently increase. To determine how dopamine regulates food preference we performed 6-hydroxydopamine (6-OHDA) lesions, depleting dopamine in specific brain regions in male Sprague Dawley rats. Food preference was assessed by providing the rats with free choice access to control diet, fat, 20% sucrose and tap water. Rats with midbrain lesions targeting the substantia nigra (which is also a model of Parkinson's disease) consumed fewer calories, as reflected by a decrease in control diet intake, but they surprisingly displayed an increase in fat intake, without change in the sucrose solution intake compared to sham animals. To determine which of the midbrain dopamine projections may contribute to this effect, we next compared the impact of 6-OHDA lesions of terminal fields, targeting the dorsal striatum, the lateral nucleus accumbens and the medial nucleus accumbens. We found that 6-OHDA lesion of the lateral nucleus accumbens, but not of the dorsal striatum or the medial nucleus accumbens, led to increased fat intake. These findings indicate a role for lateral nucleus accumbens dopamine in regulating food preference, in particular the intake of fat.

Diet-induced changes in the Lean Brain: Hypercaloric high-fat-high-sugar snacking decreases serotonin transporters in the human hypothalamic region.

It is evident that there is a relationship between the brain's serotonin system and obesity. Although it is clear that drugs affecting the serotonin system regulate appetite and food intake, it is unclear whether changes in the serotonin system are cause or consequence of obesity. To determine whether obesogenic eating habits result in reduced serotonin transporter (SERT)-binding in the human hypothalamic region, we included 25 lean, male subjects who followed a 6-week-hypercaloric diet, which were high-fat-high-sugar (HFHS) or high-sugar (HS) with increased meal size or -frequency (=snacking pattern). We measured SERT-binding in the hypothalamic region with SPECT. All hypercaloric diets significantly increased body weight by 3-3.5%. Although there were no differences in total calories consumed between the diets, only a hypercaloric HFHS-snacking diet decreased SERT-binding significantly by 30%. We here show for the first time in humans that snacking may change the serotonergic system increasing the risk to develop obesity.