Metabolic hormones, dopamine circuits, and feeding

Department of Neurology, Yale University School of Medicine, USA.
Frontiers in Neuroendocrinology (Impact Factor: 7.04). 10/2009; 31(1):104-12. DOI: 10.1016/j.yfrne.2009.10.004
Source: PubMed


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.

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Available from: Nandakumar S Narayanan
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    • "Several determinants of feeding behavior have been studied extensively and encompass the homeostatic regulation of nutrient intake, generally attributed to hypothalamic brainstem circuitry (Saper et al., 2002). Non-homeostatic feeding is, in part, a consequence of the potent reinforcing and motivational properties of food tied closely 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 highfat , nutrient-rich food is essentially ubiquitous in developed countries, not all individuals with access to these foods consume them in excess or become obese. "
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    ABSTRACT: Feeding behavior is exquisitely regulated by homeostatic and hedonic neural substrates that integrate energy demand as well as the reinforcing and rewarding aspects of food. Understanding the net contribution of homeostatic and reward-driven feeding has become critical because of the ubiquitous source of energy-dense foods and the consequent obesity epidemic. Hypothalamic agouti-related peptide-secreting neurons (AgRP neurons) provide the primary orexigenic drive of homeostatic feeding. Using models of neuronal inhibition or ablation, we demonstrate that the feeding response to a fast ghrelin or serotonin receptor agonist relies on AgRP neurons. However, when palatable food is provided, AgRP neurons are dispensable for an appropriate feeding response. In addition, AgRP-ablated mice present exacerbated stress-induced anorexia and palatable food intake-a hallmark of comfort feeding. These results suggest that, when AgRP neuron activity is impaired, neural circuits sensitive to emotion and stress are engaged and modulated by food palatability and dopamine signaling. Copyright © 2015 Elsevier Inc. All rights reserved.
    Full-text · Article · Aug 2015 · Cell metabolism
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    • "mbic DA release and contributes to the development of obesity ( Fulton et al . , 2006 ; Leinninger et al . , 2009 ) . Feeding peptides can also directly modulate the activity of mesolimbic DA neurons . For example , DA neurons in the VTA express receptors to leptin ( Hommel et al . , 2006 ) , ghrelin , insulin , orexin , melanocortin and GLP - 1 ( Narayanan et al . , 2010 ; Dossat et al . , 2011 ; Dossat et al . , 2013 ) . Furthermore , orexigenic peptides like ghrelin increase the activity of VTA DA cells and increase DA release in the NAc when exposed to food stimuli ( Jerlhag et al . , 2012 ; Skibicka et al . , 2013 ) , potentiating an increase in food intake . In contrast , anorexigenic peptides like"
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    ABSTRACT: Hunger, mostly initiated by a deficiency in energy, induces food seeking and intake. However, the drive toward food is not only regulated by physiological needs, but is motivated by the pleasure derived from ingestion of food, in particular palatable foods. Therefore, feeding is viewed as an adaptive motivated behavior that involves integrated communication between homeostatic feeding circuits and reward circuits. The initiation and termination of a feeding episode are instructed by a variety of neuronal signals, and maladaptive plasticity in almost any component of the network may lead to the development of pathological eating disorders. In this review we will summarize the latest understanding of how the feeding circuits and reward circuits in the brain interact. We will emphasize communication between the hypothalamus and the mesolimbic dopamine system and highlight complexities, discrepancies, open questions and future directions for the field.
    Full-text · Article · Apr 2015
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    • "The VTA contains a large population of dopamine (DA) neurons that project to sites throughout the brain that regulate feeding, food reinforcement, and motivated behavior [see (Baik, 2013; Narayanan et al, 2010; Vucetic and Reyes, 2010) for review]. In particular, phasic " spikes " in DA release in the nucleus accumbens (NAc) evoked by aspects of food reward (Brown et al, 2011; Roitman et al, 2004) have been shown to be modulated by feeding-related hormones (Cone et al, 2014) and are sufficient for food reinforcement (Domingos et al, 2011). "
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    ABSTRACT: Amylin acts in the CNS to reduce feeding and body weight. Recently, the ventral tegmental area (VTA), a mesolimbic nucleus important for food intake and reward, was identified as a site-of-action mediating the anorectic effects of amylin. However, the long-term physiological relevance and mechanisms mediating the intake-suppressive effects of VTA amylin receptor activation are unknown. Data show that the core component of the amylin receptor, the calcitonin receptor (CTR), is expressed on VTA dopamine neurons and that activation of VTA amylin receptors reduces phasic dopamine in the nucleus accumbens core (NAcC). Suppression in NAcC dopamine mediates VTA amylin-induced hypophagia, as combined NAcC D1/D2 receptor agonists block the intake-suppressive effects of VTA amylin receptor activation. Knockdown of VTA CTR via AAV-shRNA resulted in hyperphagia and exacerbated body weight gain in rats maintained on high-fat diet. Collectively, findings show that VTA amylin receptor signaling controls energy balance by modulating mesolimbic dopamine signaling.Neuropsychopharmacology accepted article preview online, 18 July 2014; doi:10.1038/npp.2014.180.
    Full-text · Article · Jul 2014 · Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology
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