Early-life stress is correlated with the development of anxiety-related behavior in adolescence, but underlying mechanisms remain poorly known. The α_1A-adrenergic receptor (AR) is linked to mood regulation and its function is assumed to be regulated by β-arrestins (βArrs) via desensitization and downregulation. Here, we investigated correlation between changes in α_1A-AR and βArr2 levels in the prefrontal cortex (PFC) and hippocampus of adolescent and adult male rats subjected to maternal separation (MS) and their relationship with anxiety-like behavior in adolescence. MS was performed 3 h per day from postnatal days 2–11 and anxiety-like behavior was evaluated in the elevated plus-maze and open field tests. The protein levels were examined using western blot assay. MS decreased α_1A-AR expression and increased βArr2 expression in both brain regions of adolescent rats, while induced reverse changes in adulthood. MS adolescent rats demonstrated higher anxiety-type behavior and lower activity in behavioral tests than controls. Decreased α_1A-AR levels in MS adolescence strongly correlated with reduced time spent in the open field central area, consistent with increased anxiety-like behavior. An anxiety-like phenotype was mimicked by acute and chronic treatment of developing rats with prazosin, an α_1A-AR antagonist, suggesting α_1A-AR downregulation may facilitate anxiety behavior in MS adolescent rats. Together, our results indicate a negative correlation between α_1A-AR neurotransmission and βArr2 levels in both adults and anxious-adolescent rats and suggest that increased βArr2 levels may contribute to posttranslational regulation of α_1A-AR and modulation of anxiety-like behavior in adolescent rats. This may provide a path to develop more effective anxiolytic treatments.

早年生活压力与青春期焦虑相关行为的发展相关，但其潜在机制仍知之甚少。α _1A -肾上腺素能受体 (AR) 与情绪调节有关，其功能被认为受 β-抑制蛋白 (βArrs) 通过脱敏和下调调节。_{在这里，我们调查了经历母体分离 (MS) 的青春期和成年雄性大鼠前额叶皮层 (PFC) 和海马体中 α 1A} -AR 和 βArr2 水平变化之间的相关性，以及它们与青春期焦虑样行为的关系。从产后第 2-11 天开始，每天进行 3 小时 MS，并在高架十字迷宫和开放场地测试中评估焦虑样行为。使用蛋白质印迹测定检查蛋白质水平。MS 降低 α_1A -AR 表达和增加的 βArr2 表达在青春期大鼠的两个大脑区域，同时在成年期诱导反向变化。与对照组相比，MS 青春期大鼠在行为测试中表现出更高的焦虑型行为和更低的活动。MS 青春期降低的 α _1A -AR 水平与花在开放区域中心区域的时间减少密切相关，这与焦虑样行为的增加一致。用哌唑嗪（一种 α _1A -AR 拮抗剂）对发育中的大鼠进行急性和慢性治疗可模拟类似焦虑的表型，表明 α _1A -AR 下调可能促进 MS 青春期大鼠的焦虑行为。总之，我们的结果表明 α _{1A之间呈负相关}-AR 神经传递和 βArr2 水平在成年和焦虑的青春期大鼠中，表明增加的 βArr2 水平可能有助于 α _1A -AR 的翻译后调节和青春期大鼠焦虑样行为的调节。这可能会为开发更有效的抗焦虑疗法提供途径。