title: Amylin modulates the mesolimbic dopamine system to control energy balance.
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 (AmyR) activation are unknown. Data show that the core component of the AmyR, the calcitonin receptor (CTR), is expressed on VTA dopamine (DA) neurons and that activation of VTA AmyRs reduces phasic DA in the nucleus accumbens core (NAcC). Suppression in NAcC DA mediates VTA amylin-induced hypophagia, as combined NAcC D1/D2 receptor agonists block the intake-suppressive effects of VTA AmyR activation. Knockdown of VTA CTR via adeno-associated virus short hairpin RNA resulted in hyperphagia and exacerbated body weight gain in rats maintained on high-fat diet. Collectively, these findings show that VTA AmyR signaling controls energy balance by modulating mesolimbic DA signaling.
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Elizabeth G
authors.initials: EG
authors.lastname: Mietlicki-Baase
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Reiner
authors.affiliation: Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Jackson J
authors.initials: JJ
authors.lastname: Cone
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Diana R
authors.initials: DR
authors.lastname: Olivos
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: McGrath
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Zimmer
authors.affiliation: Department of Psychology, University of Illinois at Chicago, Chicago, IL, USA.
authors.forename: Mitchell F
authors.initials: MF
authors.lastname: Roitman
authors.affiliation: Translational Neuroscience Program, Department of Psychiatry, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Hayes
mesh_terms: D065091:Amylin Receptor Agonists / Q000494:pharmacology*; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology*; D059305:Diet, High-Fat; D004298:Dopamine / Q000378:metabolism*; D004435:Eating / Q000187:drug effects / Q000502:physiology; D058228:Islet Amyloid Polypeptide / Q000494:pharmacology*; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018003:Receptors, Calcitonin / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D017447:Receptors, Dopamine D1 / Q000819:agonists / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000819:agonists / Q000378:metabolism; D058287:Receptors, Islet Amyloid Polypeptide / Q000378:metabolism; D017557:Ventral Tegmental Area / Q000187:drug effects* / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects / Q000502:physiology
chemical_list: D065091:Amylin Receptor Agonists; D001067:Appetite Depressants; D058228:Islet Amyloid Polypeptide; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D058287:Receptors, Islet Amyloid Polypeptide; D004298:Dopamine