Abstract | BACKGROUND: METHODS: Behavioral, histological, mass spectrometry imaging, and biosensor-mediated measures of glutamate were conducted with MAOIs in wild-type and TAAR1-knockout (KO) mice. RESULTS: Both antidepressant and locomotion responses to TCP were enhanced in TAAR1-KO mice. A recently developed fluoromethylpyridinium-based mass spectrometry imaging method revealed robust accumulation of striatal tyramine on TCP administration. Furthermore, tyramine accumulation was higher in TAAR1-KO versus wild-type mice, suggesting a negative feedback mechanism for TAAR1 in sensing tyramine levels. Combined histoenzymological and immunohistological studies revealed hitherto unknown TAAR1 localization in brain areas projecting to the substantia nigra/ventral tegmental area. Using an enzyme-based biosensor technology, we found that both TCP and tyramine reduced glutamate release in the substantia nigra in wild-type but not in TAAR1-KO mice. Moreover, glutamate measures in freely moving animals treated with TCP demonstrated that TAAR1 prevents glutamate accumulation in the substantia nigra during hyperlocomotive states. CONCLUSIONS: These observations suggest that tyramine, in interaction with glutamate, is involved in centrally mediated behavioral, transcriptional, and neurochemical effects of MAOIs.
|
Authors | Ioannis Mantas, Theodosia Vallianatou, Yunting Yang, Mohammadreza Shariatgorji, Maria Kalomoiri, Elva Fridjonsdottir, Mark J Millan, Xiaoqun Zhang, Per E Andrén, Per Svenningsson |
Journal | Biological psychiatry
(Biol Psychiatry)
Vol. 90
Issue 1
Pg. 16-27
(07 01 2021)
ISSN: 1873-2402 [Electronic] United States |
PMID | 33579534
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
|
Copyright | Copyright © 2020 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved. |
Chemical References |
- Monoamine Oxidase Inhibitors
- Receptors, G-Protein-Coupled
- Glutamic Acid
- Monoamine Oxidase
- Tyramine
- Trace amine-associated receptor 1
|
Topics |
- Animals
- Glutamic Acid
- Mice
- Mice, Knockout
- Monoamine Oxidase
- Monoamine Oxidase Inhibitors
(pharmacology)
- Receptors, G-Protein-Coupled
(physiology)
- Tyramine
|