Central Amygdala Prepronociceptin-Expressing Neurons Mediate Palatable Food Consumption and Reward

J Andrew Hardaway; Lindsay R Halladay; Christopher M Mazzone; Dipanwita Pati; Daniel W Bloodgood; Michelle Kim; Jennifer Jensen; Jeffrey F DiBerto; Kristen M Boyt; Ami Shiddapur; Ava Erfani; Olivia J Hon; Sofia Neira; Christina M Stanhope; Jonathan A Sugam; Michael P Saddoris; Greg Tipton; Zoe McElligott; Thomas C Jhou; Garret D Stuber; Michael R Bruchas; Cynthia M Bulik; Andrew Holmes; Thomas L Kash

doi:10.1016/j.neuron.2019.03.037

Central Amygdala Prepronociceptin-Expressing Neurons Mediate Palatable Food Consumption and Reward

Neuron. 2019 Jun 5;102(5):1037-1052.e7. doi: 10.1016/j.neuron.2019.03.037. Epub 2019 Apr 24.

Authors

J Andrew Hardaway¹, Lindsay R Halladay², Christopher M Mazzone³, Dipanwita Pati⁴, Daniel W Bloodgood³, Michelle Kim⁴, Jennifer Jensen⁴, Jeffrey F DiBerto⁴, Kristen M Boyt⁴, Ami Shiddapur⁴, Ava Erfani⁴, Olivia J Hon³, Sofia Neira³, Christina M Stanhope⁴, Jonathan A Sugam⁴, Michael P Saddoris⁵, Greg Tipton⁴, Zoe McElligott⁶, Thomas C Jhou⁷, Garret D Stuber⁸, Michael R Bruchas⁹, Cynthia M Bulik¹⁰, Andrew Holmes¹¹, Thomas L Kash¹²

Affiliations

¹ Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: hardawayja@gmail.com.
² Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA; Department of Psychology, Santa Clara University, Santa Clara, CA 95053, USA.
³ Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
⁴ Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
⁵ Department of Psychology and Neuroscience, University of Colorado, Boulder, Boulder, CO 80309, USA.
⁶ Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
⁷ Department of Neuroscience, Medical University of South Carolina, Charleston, SC 29425, USA.
⁸ Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.
⁹ Division of Basic Research, Department of Anesthesiology, Washington University in St. Louis School of Medicine, St. Louis, MO 63110, USA; Center for Neurobiology of Addiction, Pain, and Emotion, University of Washington, Seattle, WA 98195, USA; Department of Anesthesiology and Pain Medicine, University of Washington, Seattle, WA 98195, USA; Department of Pharmacology, University of Washington, Seattle, WA 98195, USA.
¹⁰ Department of Psychiatry, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
¹¹ Laboratory of Behavioral and Genomic Neuroscience, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, USA.
¹² Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA; Department of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA. Electronic address: thomas_kash@med.unc.edu.

Abstract

Food palatability is one of many factors that drives food consumption, and the hedonic drive to feed is a key contributor to obesity and binge eating. In this study, we identified a population of prepronociceptin-expressing cells in the central amygdala (Pnoc^CeA) that are activated by palatable food consumption. Ablation or chemogenetic inhibition of these cells reduces palatable food consumption. Additionally, ablation of Pnoc^CeA cells reduces high-fat-diet-driven increases in bodyweight and adiposity. Pnoc^CeA neurons project to the ventral bed nucleus of the stria terminalis (vBNST), parabrachial nucleus (PBN), and nucleus of the solitary tract (NTS), and activation of cell bodies in the central amygdala (CeA) or axons in the vBNST, PBN, and NTS produces reward behavior but did not promote feeding of palatable food. These data suggest that the Pnoc^CeA network is necessary for promoting the reinforcing and rewarding properties of palatable food, but activation of this network itself is not sufficient to promote feeding.

Keywords: binge eating; central amygdala; nociceptin; nucleus of the solitary tract; obesity; parabrachial nucleus; reward.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Adiposity
Animals
Body Weight
Central Amygdaloid Nucleus / metabolism*
Central Amygdaloid Nucleus / physiology
Diet, High-Fat
Feeding Behavior / physiology*
Mice
Neural Pathways
Neurons / metabolism*
Neurons / physiology
Parabrachial Nucleus / metabolism
Parabrachial Nucleus / physiology
Patch-Clamp Techniques
Protein Precursors / genetics
Protein Precursors / metabolism*
Receptors, Opioid / genetics
Receptors, Opioid / metabolism*
Reward*
Septal Nuclei / metabolism
Septal Nuclei / physiology
Solitary Nucleus / metabolism
Solitary Nucleus / physiology

Substances

Protein Precursors
Receptors, Opioid
prepronociceptin

Abstract

Publication types

MeSH terms

Substances

Grants and funding