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Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants

Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-...

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Autores principales: Mantas, Ioannis, Millan, Mark J., Di Cara, Benjamin, Groenink, Lucianne, Veiga, Sylvie, Cistarelli, Laetitia, Brocco, Mauricette, Bertrand, Marc, Svenningsson, Per, Zhang, Xiaoqun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396211/
https://www.ncbi.nlm.nih.gov/pubmed/34445611
http://dx.doi.org/10.3390/ijms22168907
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author Mantas, Ioannis
Millan, Mark J.
Di Cara, Benjamin
Groenink, Lucianne
Veiga, Sylvie
Cistarelli, Laetitia
Brocco, Mauricette
Bertrand, Marc
Svenningsson, Per
Zhang, Xiaoqun
author_facet Mantas, Ioannis
Millan, Mark J.
Di Cara, Benjamin
Groenink, Lucianne
Veiga, Sylvie
Cistarelli, Laetitia
Brocco, Mauricette
Bertrand, Marc
Svenningsson, Per
Zhang, Xiaoqun
author_sort Mantas, Ioannis
collection PubMed
description Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice. Irrespective of genotype, systemic administration of o-PIT led to a similar increase in mouse brain concentrations. Consistent with the observation of a high density of TAAR1 in the medial preoptic area, o-PIT-induced hypothermia was significantly reduced in TAAR1-KO mice. Furthermore, the inhibition of a prepulse inhibition response by o-PIT, as well as its induction of striatal tyrosine hydroxylase phosphorylation and elevation of extracellular DA in prefrontal cortex, were all reduced in TAAR1-KO compared to wildtype mice. O-PIT was active in both forced-swim and marble-burying tests, and its effects were significantly blunted in TAAR1-KO mice. Conversely, the actions on behaviour and prefrontal cortex dialysis of a broad suite of clinically used antidepressants were unaffected in TAAR1-KO mice. In conclusion, o-PIT is a useful tool for exploring the hypothermic and other functional antidepressant roles of TAAR1. By contrast, clinically used antidepressants do not require TAAR1 for expression of their antidepressant properties.
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spelling pubmed-83962112021-08-28 Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants Mantas, Ioannis Millan, Mark J. Di Cara, Benjamin Groenink, Lucianne Veiga, Sylvie Cistarelli, Laetitia Brocco, Mauricette Bertrand, Marc Svenningsson, Per Zhang, Xiaoqun Int J Mol Sci Article Trace Amine-Associated Receptor 1 (TAAR1) is a potential target for the treatment of depression and other CNS disorders. However, the precise functional roles of TAAR1 to the actions of clinically used antidepressants remains unclear. Herein, we addressed these issues employing the TAAR1 agonist, o-phenyl-iodotyramine (o-PIT), together with TAAR1-knockout (KO) mice. Irrespective of genotype, systemic administration of o-PIT led to a similar increase in mouse brain concentrations. Consistent with the observation of a high density of TAAR1 in the medial preoptic area, o-PIT-induced hypothermia was significantly reduced in TAAR1-KO mice. Furthermore, the inhibition of a prepulse inhibition response by o-PIT, as well as its induction of striatal tyrosine hydroxylase phosphorylation and elevation of extracellular DA in prefrontal cortex, were all reduced in TAAR1-KO compared to wildtype mice. O-PIT was active in both forced-swim and marble-burying tests, and its effects were significantly blunted in TAAR1-KO mice. Conversely, the actions on behaviour and prefrontal cortex dialysis of a broad suite of clinically used antidepressants were unaffected in TAAR1-KO mice. In conclusion, o-PIT is a useful tool for exploring the hypothermic and other functional antidepressant roles of TAAR1. By contrast, clinically used antidepressants do not require TAAR1 for expression of their antidepressant properties. MDPI 2021-08-18 /pmc/articles/PMC8396211/ /pubmed/34445611 http://dx.doi.org/10.3390/ijms22168907 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Mantas, Ioannis
Millan, Mark J.
Di Cara, Benjamin
Groenink, Lucianne
Veiga, Sylvie
Cistarelli, Laetitia
Brocco, Mauricette
Bertrand, Marc
Svenningsson, Per
Zhang, Xiaoqun
Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants
title Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants
title_full Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants
title_fullStr Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants
title_full_unstemmed Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants
title_short Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based Antidepressants
title_sort trace amine-associated receptor 1 contributes to diverse functional actions of o-phenyl-iodotyramine in mice but not to the effects of monoamine-based antidepressants
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8396211/
https://www.ncbi.nlm.nih.gov/pubmed/34445611
http://dx.doi.org/10.3390/ijms22168907
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