Metabolic hormones, dopamine circuits, and feeding

Abstract

Recent evidence has emerged demonstrating that metabolic hormones such as ghrelin and leptin can act on ventral tegmental area (VTA) midbrain dopamine neurons to influence feeding. The VTA is the origin of mesolimbic dopamine neurons that project to the nucleus accumbens (NAc) to influence behavior. While blockade of dopamine via systemic antagonists or targeted gene delete can impair food intake, local NAc dopamine manipulations have little effect on food intake. Notably, non-dopaminergic manipulations in the VTA and NAc produce more consistent effects on feeding and food choice. More recent genetic evidence supports a role for the substantia nigra-striatal dopamine pathways in food intake, while the VTA-NAc circuit is more likely involved in higher-order aspects of food acquisition, such as motivation and cue associations. This rich and complex literature should be considered in models of how peripheral hormones influence feeding behavior via action on the midbrain circuits.

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.…”

“…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.…”

Palatability Can Drive Feeding Independent of AgRP Neurons

“…Several determinants of feeding behavior have been extensively studied and encompass homeostatic regulation of nutrient intake, generally attributed to a hypothalamic-brainstem circuitry (Saper et al, 2002). Non-homeostatic feeding is, in part, a consequence of the potent reinforcing and motivational properties of food, closely tied to the release of dopamine in limbic brain regions, which is particularly stimulated by high-fat and high-sugar (HFHS) foods (Di Chiara and Imperato, 1988;Dallman et al, 2005;Narayanan et al, 2010). Although the presence of high-fat, nutrient-rich food is essentially ubiquitous in developed countries, not all individuals with access to these foods consume them in excess or become obese.…”