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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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8907 |
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| author | Ioannis Mantas Mark J. Millan Benjamin Di Cara Lucianne Groenink Sylvie Veiga Laetitia Cistarelli Mauricette Brocco Marc Bertrand Per Svenningsson Xiaoqun Zhang |
| author_facet | Ioannis Mantas Mark J. Millan Benjamin Di Cara Lucianne Groenink Sylvie Veiga Laetitia Cistarelli Mauricette Brocco Marc Bertrand Per Svenningsson Xiaoqun Zhang |
| author_sort | Ioannis Mantas |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T08:44:09Z |
| format | Article |
| id | doaj.art-a7815438dcb04b6cb55ce7eb03e7bf54 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:09Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-a7815438dcb04b6cb55ce7eb03e7bf542023-11-22T08:02:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216890710.3390/ijms22168907Trace Amine-Associated Receptor 1 Contributes to Diverse Functional Actions of O-Phenyl-Iodotyramine in Mice but Not to the Effects of Monoamine-Based AntidepressantsIoannis Mantas0Mark J. Millan1Benjamin Di Cara2Lucianne Groenink3Sylvie Veiga4Laetitia Cistarelli5Mauricette Brocco6Marc Bertrand7Per Svenningsson8Xiaoqun Zhang9Department of Clinical Neuroscience, Karolinska Institute, 17177 Stockholm, SwedenNeuroscience and Inflammation Therapeutic Area, Institut de Recherches SERVIER, 78290 Croissy-sur-Seine, FranceNeuroscience and Inflammation Therapeutic Area, Institut de Recherches SERVIER, 78290 Croissy-sur-Seine, FranceDepartment of Pharmacology, Utrecht Institute for Pharmaceutical Sciences, 3584 CS Utrecht, The NetherlandsNeuroscience and Inflammation Therapeutic Area, Institut de Recherches SERVIER, 78290 Croissy-sur-Seine, FranceNeuroscience and Inflammation Therapeutic Area, Institut de Recherches SERVIER, 78290 Croissy-sur-Seine, FranceNeuroscience and Inflammation Therapeutic Area, Institut de Recherches SERVIER, 78290 Croissy-sur-Seine, FranceTechnologie Servier, 45000 Orléans, FranceDepartment of Clinical Neuroscience, Karolinska Institute, 17177 Stockholm, SwedenDepartment of Clinical Neuroscience, Karolinska Institute, 17177 Stockholm, SwedenTrace 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.https://www.mdpi.com/1422-0067/22/16/8907TAAR1o-PITDAantidepressants |
| spellingShingle | Ioannis Mantas Mark J. Millan Benjamin Di Cara Lucianne Groenink Sylvie Veiga Laetitia Cistarelli Mauricette Brocco Marc Bertrand Per Svenningsson Xiaoqun Zhang 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 International Journal of Molecular Sciences TAAR1 o-PIT DA 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 | TAAR1 o-PIT DA antidepressants |
| url | https://www.mdpi.com/1422-0067/22/16/8907 |
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