Alpha 1A‐Adrenergic Receptor Signaling Promotes Antidepressant‐Like Behavior and Increased Anxiety in the Mouse

Norepinephrine plays a role in the regulation of antidepressant behavior. In the present study, we used mice expressing constitutively active mutant α 1A ‐adrenergic receptors (CAM α 1A ‐ARs) to examine the effects of α 1A ‐AR signaling on behavioral depression and anxiety. CAM α 1A ‐AR mice exhibited significantly less immobility than nontransgenic mice in the tail suspension test (TST) indicating that α 1A ‐AR signaling promotes antidepressant‐like behavior. WAY100635 (5‐HT 1A receptor antagonist) potentiated the antidepressant‐like effect of CAM α 1A ‐AR expression but had no effect on nontransgenic mice. Distance traveled in the open field did not differ between CAM α 1A ‐AR mice and nontransgenic mice confirming that decreased immobility in the TST was not caused by differences in overall motor activity. However, CAM α 1A ‐AR mice spent significantly less time than nontransgenic mice in the center of the open field suggesting that α 1A ‐AR signaling is anxiogenic. We used the elevated plus maze to confirm the anxiogenic effect of α 1A ‐AR signaling. CAM α 1A ‐AR mice spent significantly more time than nontransgenic mice in the enclosed arms of the maze and had fewer entries than nontransgenic mice into the open arms. Our data indicate that α 1A ‐AR signaling promotes antidepressant‐like behavior and is anxiogenic. (This study was supported by a Bower, Bennet, & Bennet Endowed Research Chair Award from Ohio Northern University).