Negative relationship between brain α 1A -AR neurotransmission and βArr2 levels in anxious adolescent rats subjected to early life stress

• Published in: Experimental brain research 2020-12, Vol.238 (12), p.2833
• Main Authors: Mahmoodkhani, Maryam, Amini, Mohammad, Derafshpour, Leila, Ghasemi, Maedeh, Mehranfard, Nasrin
• Format: Article
• Language: English
• Subjects: Animals; Anxiety - etiology; Behavior, Animal; beta-Arrestin 2; Brain; Male; Maternal Deprivation; Rats; Receptors, Adrenergic; Stress, Psychological - complications; Synaptic Transmission
• ISSN: 1432-1106
• DOI: 10.1007/s00221-020-05937-1

Early-life stress is correlated with the development of anxiety-related behavior in adolescence, but underlying mechanisms remain poorly known. The α -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 -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 -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 -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 -AR antagonist, suggesting α -AR downregulation may facilitate anxiety behavior in MS adolescent rats. Together, our results indicate a negative correlation between α -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 -AR and modulation of anxiety-like behavior in adolescent rats. This may provide a path to develop more effective anxiolytic treatments.