title: Effects of Trace Amine-associated Receptor 1 Agonists on the Expression, Reconsolidation, and Extinction of Cocaine Reward Memory.
abstract: As a modulator of dopaminergic system, trace amine-associated receptor 1 has been shown to play a critical role in regulating the rewarding properties of additive drugs. It has been demonstrated that activation of trace amine-associated receptor 1 decreased the abuse-related behaviors of cocaine in rats. However, the role of trace amine-associated receptor 1 in specific stages of cocaine reward memory is still unclear.
  
  
  
  Here, using a cocaine-induced conditioned place preference model, we tested the effects of a selective trace amine-associated receptor 1 agonist RO5166017 on the expression, reconsolidation, and extinction of cocaine reward memory.
  
  
  
  We found that RO5166017 inhibited the expression but not retention of cocaine-induced conditioned place preference. RO5166017 had no effect on the reconsolidation of cocaine reward memory. Pretreatment with RO5166017 before extinction hindered the formation of extinction long-term memory. RO5166017 did not affect the movement during the conditioned place preference test, indicating the inhibitory effect of RO5166017 on the expression of cocaine-induced conditioned place preference was not caused by locomotion inhibition. Using a cocaine i.v. self-administration model, we found that the combined trace amine-associated receptor 1 partial agonist RO5263397 with extinction had no effect on the following cue- and drug-induced reinstatement of cocaine-seeking behavior. Repeated administration of the trace amine-associated receptor 1 agonist during extinction showed a continually inhibitory effect on the expression of cocaine reward memory both in cocaine-induced conditioned place preference and cocaine self-administration models.
  
  
  
  Taken together, these results indicate that activation of trace amine-associated receptor 1 specifically inhibited the expression of cocaine reward memory. The inhibitory effect of trace amine-associated receptor 1 agonists on cocaine reward memory suggests that trace amine-associated receptor 1 agonists could be a promising agent to prevent cocaine relapse.
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY (Drs Liu, Thorn, and Li); Research Triangle Institute, Research Triangle Park, NC (Dr Zhang).
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY (Drs Liu, Thorn, and Li); Research Triangle Institute, Research Triangle Park, NC (Dr Zhang).
authors.forename: David A
authors.initials: DA
authors.lastname: Thorn
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY (Drs Liu, Thorn, and Li); Research Triangle Institute, Research Triangle Park, NC (Dr Zhang).
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, NY (Drs Liu, Thorn, and Li); Research Triangle Institute, Research Triangle Park, NC (Dr Zhang). junxuli@buffalo.edu.
authors.forename: Jun-Xu
authors.initials: JX
authors.lastname: Li
mesh_terms: D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D058999:Drug-Seeking Behavior / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects*; D008124:Locomotion / Q000187:drug effects; D008297:Male; D008568:Memory / Q000187:drug effects*; D010080:Oxazoles / Q000494:pharmacology*; D010627:Phenethylamines / Q000494:pharmacology*; D051381:Rats; D043562:Receptors, G-Protein-Coupled / Q000819:agonists*; D012201:Reward; D012646:Self Administration; D000095383:Trace Amine-Associated Receptors
chemical_list: D003042:Cocaine; D010080:Oxazoles; D010627:Phenethylamines; D043562:Receptors, G-Protein-Coupled; D000095383:Trace Amine-Associated Receptors; C000596180:4-(3-fluoro-2-methylphenyl)-4,5-dihydrooxazol-2-ylamine; C583451:RO5166017
keywords: TAAR1; cocaine reward memory; expression; extinction; reconsolidation
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