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Interaction between the trace amine-associated receptor 1 and the dopamine D2 receptor controls cocaine’s neurochemical actions


Asif-Malik, A and Hoener, MC and Canales, JJ, Interaction between the trace amine-associated receptor 1 and the dopamine D2 receptor controls cocaine's neurochemical actions, Scientific Reports, 7, (1) Article 13901. ISSN 2045-2322 (2017) [Refereed Article]


Copyright Statement

© 2017 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0)

DOI: doi:10.1038/s41598-017-14472-z


Recent evidence suggests that the trace amine-associated receptor 1 (TAAR1) plays a pivotal role in the regulation of dopamine (DA) transmission and cocaine’s actions. However, the underlying mechanisms through which TAAR1 activation mediates these efects have not yet been elucidated. Here, we used fast-scan cyclic voltammetry to measure DA dynamics and explore such mechanisms. We show, frst, that the full TAAR1 agonist, RO5256390, dose-dependently blocked cocaine-induced inhibition of DA clearance in slices of the nucleus accumbens. Second, subthreshold inhibition of PKA or PKC phosphorylation did not prevent TAAR1 suppression of cocaine efects whereas subefective doses of the DA D2 receptor antagonist, L-741,626, rescued cocaine’s ability to produce changes in DA uptake in the presence of full TAAR1 activation, thus indicating that TAAR1 modulation of cocaine efects requires simultaneous DA D2 receptor activation. Predictably, inhibition of glycogen synthase kinase-3 (GSK-3), which results from activation of D2/TAAR1 heterodimers, fully reproduced the inhibitory efects of TAAR1 activation on cocaine-induced changes in DA transmission. Collectively, the present observations reveal that the ability of TAAR1 to regulate cocaine efects is linked to cooperative interactions with D2 autoreceptors and associated downstream molecular targets converging on GSK-3 and suggest a new mechanism to disrupt cocaine neurochemical actions.

Item Details

Item Type:Refereed Article
Keywords:dopamine, D2 receptor, cocaine, trace amine-associated receptor 1, neurochemistry, drug use
Research Division:Psychology
Research Group:Biological psychology
Research Field:Behavioural neuroscience
Objective Division:Expanding Knowledge
Objective Group:Expanding knowledge
Objective Field:Expanding knowledge in psychology
UTAS Author:Canales, JJ (Professor Juan Canales)
ID Code:125890
Year Published:2017
Web of Science® Times Cited:20
Deposited By:Psychology
Deposited On:2018-05-15
Last Modified:2018-08-13
Downloads:134 View Download Statistics

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