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The trace amine-associated receptor 1 modulates methamphetamine's neurochemical and behavioral effects

Citation

Cotter, R and Pei, Y and Mus, L and Harmeier, A and Gainetdinov, RR and Hoener, MC and Canales, JJ, The trace amine-associated receptor 1 modulates methamphetamine's neurochemical and behavioral effects, Frontiers in neuroscience, 9 Article 39. ISSN 1662-453X (2015) [Refereed Article]


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Copyright Statement

2015 Cotter, Pei, Mus, Harmeier, Gainetdinov, Hoener and Canales. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) http://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fnins.2015.00039

Abstract

The newly discovered trace amine-associated receptor 1 (TAAR1) has the ability to regulate both dopamine function and psychostimulant action. Here, we tested in rats the ability of RO5203648, a selective TAAR1 partial agonist, to modulate the physiological and behavioral effects of methamphetamine (METH). In experiment 1, RO5203468 dose- and time-dependently altered METH-induced locomotor activity, manifested as an early attenuation followed by a late potentiation of METH's stimulating effects. In experiment 2, rats received a 14-day treatment regimen during which RO5203648 was co-administered with METH. RO5203648 dose-dependently attenuated METH-stimulated hyperactivity, with the effects becoming more apparent as the treatments progressed. After chronic exposure and 3-day withdrawal, rats were tested for locomotor sensitization. RO5203648 administration during the sensitizing phase prevented the development of METH sensitization. However, RO5203648, at the high dose, cross-sensitized with METH. In experiment 3, RO5203648 dose-dependently blocked METH self-administration without affecting operant responding maintained by sucrose, and exhibited lack of reinforcing efficacy when tested as a METH's substitute. Neurochemical data showed that RO5203648 did not affect METH-mediated DA efflux and uptake inhibition in striatal synaptosomes. In vivo, however, RO5203648 was able to transiently inhibit METH-induced accumulation of extracellular DA levels in the nucleus accumbens. Taken together, these data highlight the significant potential of TAAR1 to modulate METH's neurochemical and behavioral effects.

Item Details

Item Type:Refereed Article
Keywords:methamphetamine; microdialysis; self-administration; sensitization; synaptosomes; trace amine-associated receptor
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 (Dr Juan Canales)
ID Code:121258
Year Published:2015
Web of Science® Times Cited:14
Deposited By:Psychology
Deposited On:2017-09-20
Last Modified:2017-10-19
Downloads:3 View Download Statistics

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