title: Effects of the trace amine-associated receptor 1 agonist RO5263397 on abuse-related effects of cocaine in rats.
abstract: Animal knockout studies suggest that trace amine-associated receptor (TAAR) 1 is involved in behavioral effects of psychostimulants such as cocaine. Recently, several highly selective TAAR 1 agonists have been discovered. However, little is known of the impact of TAAR 1 agonists on abuse-related effects of cocaine. Here, we report the effects of a TAAR 1 agonist RO5263397 on several abuse-related behavioral effects of cocaine in rats. RO5263397 was evaluated for its effects on cocaine-induced behavioral sensitization, conditioned place preference (CPP), cue- and cocaine prime-induced reinstatement of cocaine-seeking behavior, and cocaine self-administration using behavioral economic analysis. RO5263397 reduced the expression of cocaine behavioral sensitization, cue- and cocaine prime-induced reinstatement of cocaine seeking, and expression but not development of cocaine CPP. Behavioral economic analysis showed that RO5263397 increased the elasticity of the cocaine demand curve, but did not change cocaine consumption at minimal prices. Taken together, this is the first systematic assessment of a TAAR 1 agonist on a range of behavioral effects of cocaine, showing that RO5263397 was efficacious in reducing cocaine-mediated behaviors. Collectively, these data uncover essential neuromodulatory roles of TAAR 1 on cocaine abuse, and suggest that TAAR 1 may represent a novel drug target for the treatment of cocaine addiction.
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Thorn
authors.affiliation: 1] Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY, USA [2] Department of Physiology and Pathophysiology, Tianjin Medical University, Tianjin, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jing
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: Amy M
authors.initials: AM
authors.lastname: Gancarz-Kausch
authors.affiliation: Department of Psychology, College of Charleston, Charleston, SC, USA.
authors.forename: Chad M
authors.initials: CM
authors.lastname: Galuska
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Dietz
authors.affiliation: Research Triangle Institute, Research Triangle Park, NC, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, The State University of New York, Buffalo, NY, USA.
authors.forename: Jun-Xu
authors.initials: JX
authors.lastname: Li
mesh_terms: D000818:Animals; D003042:Cocaine / Q000008:administration & dosage; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003463:Cues; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage; D058999:Drug-Seeking Behavior / Q000187:drug effects* / Q000502:physiology; D005108:Extinction, Psychological / Q000187:drug effects / Q000502:physiology; D008297:Male; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000378:metabolism; D012646:Self Administration; D013028:Space Perception / Q000187:drug effects / Q000502:physiology; D000095383:Trace Amine-Associated Receptors
chemical_list: D003042:Cocaine; D018765:Dopamine Uptake Inhibitors; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors
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