New Insights into Complex PTSD Treatment: Focus on TAAR1 Agonists
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Le résumé fourni par la source
Background/Objectives: The therapeutic potential of selective trace amine-associated receptor 1 (TAAR1) agonists has been established in multiple animal models of depression and anxiety. PTSD is a debilitating psychiatric disorder frequently characterized by anxiety and often comorbid with major depressive disorder. Complex PTSD represents an even more severe clinical presentation, emerging from prolonged or repeated exposure to traumatic events. Recent studies indicate that TAAR1 agonists can attenuate anxiety-like behaviors in experimental models of PTSD; however, the molecular mechanisms underlying this effect remain poorly understood. In this study, we evaluated whether TAAR1 agonism modulates PTSD-related neurochemical and molecular changes within the hippocampus and striatum. Methods: Post-traumatic stress was modeled using predator stress, a validated experimental paradigm relevant to complex PTSD. Treatment consisted of intraperitoneal administration of the TAAR1 agonist LK00764. Monoamine neurotransmitters and their metabolites were quantified, and the expression of genes implicated in noradrenergic, dopaminergic, and serotonergic signaling pathways was assessed. In addition, gene network reconstruction was performed using artificial intelligence to identify TAAR1-dependent regulatory interactions. Results: Treatment with a TAAR1 agonist fully prevented behavioral abnormalities in the experimental model of complex PTSD. Neurochemical analyses revealed decreased 5-HT levels in the hippocampus and reduced dopamine and metabolite concentrations in the striatum following TAAR1 agonism. Moreover, TAAR1 activation was associated with increased expression of the neurotrophic factor BDNF in the striatum. Gene network reconstruction identified a distinct molecular hub within the PTSD network, comprising TAAR1-coexpressed genes, their encoded proteins, and interconnected signaling pathways, suggesting a tightly regulated feedback loop. Conclusions: These findings provide novel evidence that TAAR1 agonists exert protective effects against complex PTSD-related behavioral and neurochemical abnormalities. The reconstructed TAAR1-centered gene network offers mechanistic insight into receptor-dependent regulation of monoaminergic signaling and neuroplasticity, supporting further exploration of TAAR1 agonists as promising therapeutic candidates for PTSD.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- New Insights into Complex PTSD Treatment: Focus on TAAR1 Agonists
- Date Crossref
- 03/12/2025
- Éditeur
- MDPI AG
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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Chelyabinsk State University pays non établi dans la noticeUniversité ou école supérieure
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South Ural State University Scientific and Innovation Activity Management pays non établi dans la noticeUniversité ou école supérieure
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Novosibirsk State Medical University pays non établi dans la noticeUniversité ou école supérieure
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Novosibirsk State University Institute of Medicine and Medical Technologies pays non établi dans la noticeUniversité ou école supérieure
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St Petersburg University pays non établi dans la noticeUniversité ou école supérieure
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Federal Research Centre of Nutrition and Biotechnology pays non établi dans la noticeStructure de recherche
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Ruđer Bošković Institute Centre for Informatics and Computing pays non établi dans la noticeStructure de recherche
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Faculty of Fundamental Medicine pays non établi dans la noticeUniversité ou école supérieure
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St. Petersburg State University Institute of Translational Biomedicine pays non établi dans la noticeUniversité ou école supérieure
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Y. M. Lopukhin Federal State Budgetary Scientific Research Center pays non établi dans la noticeStructure de recherche
Chelyabinsk State University, Scientific and Innovation Activity Management — South Ural State University et Novosibirsk State Medical University, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.