title: Dopamine signaling in the amygdala, increased by food ingestion and GLP-1, regulates feeding behavior.
abstract: Mesolimbic dopamine plays a critical role in food-related reward processing and learning. The literature focuses primarily on the nucleus accumbens as the key dopaminergic target in which enhanced dopamine signaling is associated with reward. Here, we demonstrate a novel neurobiological mechanism by which dopamine transmission in the amygdala regulates food intake and reward. We show that food intake was associated with increased dopamine turnover in the amygdala. Next, we assess the impact of direct intra-amygdala D1 and D2 receptor activation on food intake and sucrose-driven progressive ratio operant conditioning in rats. Amygdala D2 receptor activation reduced food intake and operant behavior for sucrose, whereas D2 receptor blockade increased food intake but surprisingly reduced operant behavior. In contrast, D1 receptor stimulation or blockade did not alter feeding or operant conditioning for food. The glucagon-like peptide 1 (GLP-1) system, a target for type 2 diabetes treatment, in addition to regulating glucose homeostasis, also reduces food intake. We found that central GLP-1R receptor activation is associated with elevated dopamine turnover in the amygdala, and that part of the anorexic effect of GLP-1 is mediated by D2 receptor signaling in the amygdala. Our findings indicate that amygdala dopamine signaling is activated by both food intake and the anorexic brain-gut peptide GLP-1 and that amygdala D2 receptor activation is necessary and sufficient to change feeding behavior. Collectively these studies indicate a novel mechanism by which the dopamine system affects feeding-oriented behavior at the level of the amygdala.
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Rozita H
authors.initials: RH
authors.lastname: Anderberg
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Christine
authors.initials: C
authors.lastname: Anefors
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Filip
authors.initials: F
authors.lastname: Bergquist
authors.affiliation: Department of Pharmacology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden.
authors.forename: Hans
authors.initials: H
authors.lastname: Nissbrandt
authors.affiliation: Department of Physiology, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, Sweden. Electronic address: Karolina.Skibicka@neuro.gu.se.
authors.forename: Karolina P
authors.initials: KP
authors.lastname: Skibicka
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000679:Amygdala / Q000187:drug effects / Q000502:physiology*; D000704:Analysis of Variance; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003216:Conditioning, Operant / Q000187:drug effects; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000494:pharmacology; D004435:Eating / Q000187:drug effects / Q000502:physiology*; D000077270:Exenatide; D005247:Feeding Behavior / Q000187:drug effects / Q000502:physiology*; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014688:Venoms / Q000494:pharmacology
chemical_list: D015259:Dopamine Agents; D010455:Peptides; D014688:Venoms; D015102:3,4-Dihydroxyphenylacetic Acid; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide; D004298:Dopamine
keywords: Amygdala; Dopamine; Exendin-4; Food intake; Food reward; GLP-1; Obesity