title: The Trace Amine-Associated Receptor 1 Agonist RO5256390 Blocks Compulsive, Binge-like Eating in Rats.
abstract: Compulsive, binge eating of highly palatable food constitutes a core feature of some forms of obesity and eating disorders, as well as of the recently proposed disorder of food addiction. Trace amine-associated receptor 1 (TAAR1) is a highly conserved G-protein-coupled receptor bound by endogenous trace amines. TAAR1 agonists have been shown to reduce multiple behavioral effects of drugs of abuse through their actions on the mesocorticolimbic system. In this study, we hypothesized that TAAR1 may have a role in compulsive, binge-like eating; we tested this hypothesis by assessing the effects of a TAAR1 agonist, RO5256390, in multiple excessive feeding-related behaviors induced by limiting access to a highly palatable diet in rats. Our results show that RO5256390 blocked binge-like eating in rats responding 1 h per day for a highly palatable sugary diet. Consistent with a palatability-selective effect, drug treatment selectively reduced the rate and regularity of palatable food responding, but it did not affect either baseline intake or food restriction-induced overeating of the standard chow diet. Furthermore, RO5256390 fully blocked compulsive-like eating when the palatable diet was offered in an aversive compartment of a light/dark conflict box, and blocked the conditioned rewarding properties of palatable food, as well as palatable food-seeking behavior in a second-order schedule of reinforcement. Drug treatment had no effect on either anxiety-like or depressive-like behavior, and it did not affect control performance in any of the tests. Importantly, rats exposed to palatable food showed decreased TAAR1 levels in the medial prefrontal cortex (mPFC), and RO5256390 microinfused into the infralimbic, but not prelimbic, subregion of the mPFC-reduced binge-like eating. Altogether, these results provide evidence for TAAR1 agonism as a novel pharmacological treatment for compulsive, binge eating.
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Antonio
authors.initials: A
authors.lastname: Ferragud
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Howell
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.|Graduate Program for Neuroscience, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Catherine F
authors.initials: CF
authors.lastname: Moore
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Tina L
authors.initials: TL
authors.lastname: Ta
authors.affiliation: Neuroscience, Ophthalmology and Rare Diseases Discovery & Translational Area, pRED, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd, Basel, Switzerland.
authors.forename: Marius C
authors.identifier: http://orcid.org/0000-0001-6510-6250
authors.initials: MC
authors.lastname: Hoener
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Valentina
authors.initials: V
authors.lastname: Sabino
authors.affiliation: Laboratory of Addictive Disorders, Departments of Pharmacology and Experimental Therapeutics and Psychiatry, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cottone
mesh_terms: D000818:Animals; D056912:Binge-Eating Disorder / Q000378:metabolism* / Q000517:prevention & control* / Q000523:psychology; D003192:Compulsive Behavior / Q000378:metabolism* / Q000517:prevention & control* / Q000523:psychology; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D005247:Feeding Behavior / Q000187:drug effects / Q000523:psychology; D008297:Male; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism*; D000095383:Trace Amine-Associated Receptors
chemical_list: D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors