Central dopaminergic circuitry controlling food intake and reward: implications for the regulation of obesity

Abstract

Prevalence of obesity in the general population has increased in the past 15 years from 15% to 35%. With increasing obesity, the coincident medical and social consequences are becoming more alarming. Control over food intake is crucial for the maintenance of body weight and represents an important target for the treatment of obesity. Central nervous system mechanisms responsible for control of food intake have evolved to sense the nutrient and energy levels in the organism and to coordinate appropriate responses to adjust energy intake and expenditure. This homeostatic system is crucial for maintenance of stable body weight over long periods of time of uneven energy availability. However, not only the caloric and nutritional value of food but also hedonic and emotional aspects of feeding affect food intake. In modern society, the increased availability of highly palatable and rewarding (fat, sweet) food can significantly affect homeostatic balance, resulting in dysregulated food intake. This review will focus on the role of hypothalamic and mesolimbic/mesocortical dopaminergic (DA) circuitry in coding homeostatic and hedonic signals for the regulation of food intake and maintenance of caloric balance. The interaction of dopamine with peripheral and central indices of nutritional status (e.g., leptin, ghrelin, neuropeptide Y), and the susceptibility of the dopamine system to prenatal insults will be discussed. Additionally, the importance of alterations in dopamine signaling that occur coincidently with obesity will be addressed.

Amylin Receptor Signaling in the Ventral Tegmental Area is Physiologically Relevant for the Control of Food Intake

“…Indeed, differences in intracellular or intercellular signaling pathways engaged by AP vs VTA amylin receptor populations may help to explain the disparate time courses of feeding effects obtained after AP vs VTA amylin receptor activation (Mollet et al, 2004); this is an intriguing possibility that should be tested empirically. Given the important role of mesolimbic dopamine signaling in the regulation of feeding (Narayanan et al, 2010;Vucetic and Reyes, 2010), VTA amylin-induced alterations in dopamine production or release may also mediate the feeding effects observed in the present studies, but this too remains to be examined.…”

“…As neuronal processing by the VTA is well known to affect palatable food intake (Egecioglu et al, 2011;Vucetic and Reyes, 2010), it is notable that intra-VTA amylin receptor activation not only reduced intake of standard rodent chow, but also reduced intake of a palatable sucrose solution with an extremely low dose of sCT that had no effect on chow intake following VTA delivery. Collectively, the current results show that activation of VTA amylin receptors controls food intake by influencing meal sizespecific processing.…”

“…The VTA has been recognized as an important nucleus in the control of food intake, especially palatable food intake (Narayanan et al, 2010;Vucetic and Reyes, 2010), as well as in the broader context of motivated appetitive behaviors (eg, drug taking/seeking; Schmidt et al, 2009;Self, 2004). The finding that intra-VTA amylin receptor activation reduces intake of standard chow and palatable sucrose solution, as well as self-administered sucrose pellets, offers the intriguing possibility that amylin receptor activation in the VTA may reduce motivation to obtain food.…”

“…The VTA and other structures in the mesolimbic dopamine system are important for the control of palatable food intake and food reward (Narayanan et al, 2010;Vucetic and Reyes, 2010). To investigate whether VTA amylin receptor signaling controls palatable food intake, rats habituated to a 1-h access to 15% sucrose solution received counterbalanced intra-VTA injections of sCT (0.04 or 0.01 mg) or vehicle (100 nl aCSF) just before sucrose presentation and intake was recorded every 10 min for 1 h. The doses of sCT selected were suprathreshold (0.04 mg; see Figure 2a) or subthreshold (0.01 mg; data not shown) for an effect on 1 h chow intake when delivered to the VTA.…”

“…Thus, given that energy balance control is distributed across the neuraxis (Grill, 2006), it is highly plausible that non-AP amylin-receptor expressing nuclei may mediate the energy balance effects of amylin. The ventral tegmental area (VTA), a mesolimbic structure well known to contribute to the regulation of food intake, especially intake of palatable foods (Narayanan et al, 2010;Vucetic and Reyes, 2010), has been overlooked in the amylin-feeding literature. Despite the fact that both amylin and sCT bind in the VTA (Paxinos et al, 2004), the role of VTA amylin receptor activation on food intake control has not been evaluated.…”