title: The trace amine associated receptor 1 agonist RO5263397 attenuates the induction of cocaine behavioral sensitization in rats.
abstract: The trace amine associated receptor (TAAR) 1 is a new G protein coupled receptor that critically modulates central dopaminergic system. Recently, several selective TAAR 1 ligands have been described to possess antipsychotic and antidepressant-like activities. However, it is unknown of the role of these ligands in modulating psychostimulant-induced neurobehavioral plasticity. This study examined the effects of a selective TAAR 1 agonist, RO5263397, on cocaine induced behavioral sensitization in rats, a rodent model of drug-induced behavioral plasticity. Daily treatment with 15mg/kg cocaine (i.p., 7 days) induced robust locomotor sensitization in rats. RO5263397 (1-10mg/kg, i.p.) alone did not significantly alter the locomotor activity. Acute treatment with RO5263397 (3.2 and 10mg/kg) did not significantly modify cocaine-induced hyperactivity; however, the induction of locomotor sensitization was significantly blocked after 7 days of daily RO5263397 treatment. More importantly, the expression of locomotor sensitization remained significantly attenuated when rats were re-tested 7 days after the last drug treatment. The marked attenuation of cocaine sensitization was also evidenced by the suppression of the dose-effect function (3.2-32mg/kg) of cocaine sensitization. Together, these data represent the first to report a critical modulatory role of TAAR 1 agonists in cocaine-induced behavioral plasticity, which may be indicative of its potential role for altering other long-lasting behavioral maladaptations of cocaine including drug addiction.
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, the State University of New York, Buffalo, NY 14214, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Thorn
authors.affiliation: Department of Neurology, University Hospital of Hubei University for Nationalities, Enshi, Hubei 445000,China.
authors.forename: Chaogui
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Research Triangle Institute, Research Triangle Park, NC 27709, USA.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, the State University of New York, Buffalo, NY 14214, USA. Electronic address: junxuli@buffalo.edu.
authors.forename: Jun-Xu
authors.initials: JX
authors.lastname: Li
mesh_terms: D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology*; D019970:Cocaine-Related Disorders / Q000378:metabolism / Q000523:psychology; D004305:Dose-Response Relationship, Drug; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D017207:Rats, Sprague-Dawley; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D000095383:Trace Amine-Associated Receptors
chemical_list: D000697:Central Nervous System Stimulants; D003042:Cocaine; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors
keywords: Behavioral sensitization; Cocaine; Rats; TAAR 1