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Selective activation of the trace amine-associated receptor 1 decreases cocaine's reinforcing efficacy and prevents cocaine-induced changes in brain reward thresholds

Citation

Pei, Y and Mortas, P and Hoener, MC and Canales, JJ, Selective activation of the trace amine-associated receptor 1 decreases cocaine's reinforcing efficacy and prevents cocaine-induced changes in brain reward thresholds, Progress in Neuro-Psychopharmacology and Biological Psychiatry, 63 pp. 70-75. ISSN 0278-5846 (2015) [Refereed Article]

Copyright Statement

Copyright 2015 Elsevier Inc.

DOI: doi:10.1016/j.pnpbp.2015.05.014

Abstract

The newly discovered trace amine-associated receptor 1 (TAAR1) has emerged as a promising target for medication development in stimulant addiction due to its ability to regulate dopamine (DA) function and modulate stimulants' effects. Recent findings indicate that TAAR1 activation blocks some of the abuse-related physiological and behavioral effects of cocaine. However, findings from existing self-administration studies are inconclusive due to the very limited range of cocaine unit doses tested. Here, in order to shed light on the influence of TAAR1 on cocaine's reward and reinforcement, we studied the effects of partial and full activation of TAAR1on (1) the dose-response curve for cocaine self-administration and (2) cocaine-induced changes in intracranial self-stimulation (ICSS). In the first experiment, we examined the effects of the selective full and partial TAAR1 agonists, RO5256390 and RO5203648, on self-administration of five unit-injection doses of cocaine (0.03, 0.1, 0.2, 0.45, and 1mg/kg/infusion). Both agonists induced dose-dependent downward shifts in the cocaine dose-response curve, indicating that both partial and full TAAR1 activation decrease cocaine, reinforcing efficacy. In the second experiment, RO5256390 and the partial agonist, RO5263397, dose-dependently prevented cocaine-induced lowering of ICSS thresholds. Taken together, these data demonstrated that TAAR1 stimulation effectively suppresses the rewarding and reinforcing effects of cocaine in self-administration and ICSS models, supporting the candidacy of TAAR1 as a drug discovery target for cocaine addiction.

Item Details

Item Type:Refereed Article
Keywords:Cocaine; Intracranial self-stimulation; Reward; Self-administration; Trace amine-associated receptor 1
Research Division:Psychology and Cognitive Sciences
Research Group:Psychology
Research Field:Biological Psychology (Neuropsychology, Psychopharmacology, Physiological Psychology)
Objective Division:Health
Objective Group:Public Health (excl. Specific Population Health)
Objective Field:Substance Abuse
Author:Canales, JJ (Professor Juan Canales)
ID Code:121257
Year Published:2015
Web of Science® Times Cited:22
Deposited By:Psychology
Deposited On:2017-09-20
Last Modified:2017-10-12
Downloads:0

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