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Anxiety disorders affect over 3.3% of the global population, with limited treatment options available. Both trace amine-associated receptor 1 (TAAR1) and serotonergic 2C receptor (5-HT2CR) are implicated in various emotional activities, including anxiety. This study aims to investigate the role of TAAR1/5-HT2CR in the development of anxiety-like behavior in rats induced by chronic unpredictable mild stress (CUMS), and the intervention effects of a dual agonist. A CUMS-induced rat anxiety model was established. This animal research protocol has been approved by the Yantai University Laboratory Animal Ethics Committee (animal ethics number: YTU20240110). Anxiety-like behavior was assessed using the elevated zero-maze test and open field test. Western blot analysis was employed to detect the expression of TAAR1, 5-HT2CR, and brain-derived neurotrophic factor (BDNF) proteins in the rat amygdala. To observe the effects of Taar1 and Htr2c gene on anxiety-like behavior in rats, we knocked down or overexpressed these genes in the rat basolateral amygdala (BLA). Results demonstrated that CUMS-induced anxiety significantly reduced the expression levels of TAAR1 and 5-HT2CR in the amygdala of rats. Overexpression of either Taar1 or Htr2c in the BLA ameliorated anxiety-like behavior. Conversely, knocking down Taar1 or Htr2c in the BLA exacerbated CUMS-induced anxiety-like behavior. Oral administration of PCC0105004 alleviated anxiety-like behavior in CUMS rats, while knocking down both Taar1 and Htr2c in the BLA completely abolished this effect of PCC0105004. Further investigations revealed that PCC0105004 significantly increased the expression of BDNF in the amygdala of rats. These findings indicate that TAAR1 and 5-HT2CR play crucial roles in the development of anxiety-like behavior in CUMS rats, suggesting that a dual agonist targeting TAAR1/5-HT2CR may offer a novel therapeutic strategy for anxiety disorders.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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