The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats
ABSTRACT Anxiety disorder is a persistent, widespread, and intractable mood disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine‐associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders. This study examined the...
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Wiley
2025-04-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.70068 |
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| author | Yingtian Zhang Wei Zhang Linyao Yu Yaoqin Shi Min Xu Hui Wang Chunmei Li Jingwei Tian |
| author_facet | Yingtian Zhang Wei Zhang Linyao Yu Yaoqin Shi Min Xu Hui Wang Chunmei Li Jingwei Tian |
| author_sort | Yingtian Zhang |
| collection | DOAJ |
| description | ABSTRACT Anxiety disorder is a persistent, widespread, and intractable mood disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine‐associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders. This study examined the effects and underlying mechanisms of a novel TAAR1 agonist, PCC0105004, in a rat model of CUMS‐induced anxiety‐like behavior. The elevated zero maze and open field tests test were employed to evaluate the anti–anxiety‐like activity of PCC0105004. PCC0105004 dose‐dependently attenuated anxiety‐like behaviors in rats without affecting spontaneous activity. Morphologically, PCC0104005 decreased the density of dendritic spines in the amygdala. For the mechanistic studies, whole‐genome transcriptomic analysis revealed significant differences in the patterns of amygdala gene expression in the CUMS‐induced anxiety rat model. These transcriptomic data were further confirmed by using RT‐qPCR and western blotting, further revealing alterations associated with genes (Col1a1, DCN, Ewsr1) known to regulate synaptic plasticity, and PCC0105004 was able to reverse these changes. These results suggest that PCC0105004 is a promising anxiolytic candidate for pharmacotherapy of anxiety and warrants further examination and development. |
| format | Article |
| id | doaj-art-263da5ca6fd84844a97d57eeacff4076 |
| institution | DOAJ |
| issn | 2052-1707 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj-art-263da5ca6fd84844a97d57eeacff40762025-08-20T03:10:24ZengWileyPharmacology Research & Perspectives2052-17072025-04-01132n/an/a10.1002/prp2.70068The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in RatsYingtian Zhang0Wei Zhang1Linyao Yu2Yaoqin Shi3Min Xu4Hui Wang5Chunmei Li6Jingwei Tian7School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai People's Republic of ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai People's Republic of ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai People's Republic of ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai People's Republic of ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai People's Republic of ChinaState Key Laboratory of Advanced Drug Delivery and Release Systems Yantai Shandong People's Republic of ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai People's Republic of ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University Yantai People's Republic of ChinaABSTRACT Anxiety disorder is a persistent, widespread, and intractable mood disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine‐associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders. This study examined the effects and underlying mechanisms of a novel TAAR1 agonist, PCC0105004, in a rat model of CUMS‐induced anxiety‐like behavior. The elevated zero maze and open field tests test were employed to evaluate the anti–anxiety‐like activity of PCC0105004. PCC0105004 dose‐dependently attenuated anxiety‐like behaviors in rats without affecting spontaneous activity. Morphologically, PCC0104005 decreased the density of dendritic spines in the amygdala. For the mechanistic studies, whole‐genome transcriptomic analysis revealed significant differences in the patterns of amygdala gene expression in the CUMS‐induced anxiety rat model. These transcriptomic data were further confirmed by using RT‐qPCR and western blotting, further revealing alterations associated with genes (Col1a1, DCN, Ewsr1) known to regulate synaptic plasticity, and PCC0105004 was able to reverse these changes. These results suggest that PCC0105004 is a promising anxiolytic candidate for pharmacotherapy of anxiety and warrants further examination and development.https://doi.org/10.1002/prp2.70068amygdalaanxietyPCC0105004synaptic plasticityTAAR1 |
| spellingShingle | Yingtian Zhang Wei Zhang Linyao Yu Yaoqin Shi Min Xu Hui Wang Chunmei Li Jingwei Tian The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats Pharmacology Research & Perspectives amygdala anxiety PCC0105004 synaptic plasticity TAAR1 |
| title | The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats |
| title_full | The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats |
| title_fullStr | The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats |
| title_full_unstemmed | The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats |
| title_short | The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety‐Like Behaviors in Rats |
| title_sort | taar1 agonist pcc0105004 regulates amygdala synaptic plasticity to alleviate anxiety like behaviors in rats |
| topic | amygdala anxiety PCC0105004 synaptic plasticity TAAR1 |
| url | https://doi.org/10.1002/prp2.70068 |
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