Roman Tashev1, Margarita Ivanova2. 1. Department of Pathophysiology, Medical University of Sofia, Sofia, Bulgaria; Department of Behaviour Neurobiology, Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. Electronic address: msvelikova@yahoo.com. 2. Department of Physiology and Pathophysiology, Medical University, Varna, Bulgaria. Electronic address: margarita.stefanova@mu-varna.bg.
Abstract
BACKGROUND: Accumulated evidence suggests that the enhanced brain angiotensin II (Ang II) activity is associated with stress and anxiety. More recent reports demonstrated that Ang II function is elevated in depression, but the role of hippocampal Ang II and its receptors in this state is not well established. The present study investigated the effects of Ang II and losartan (a selective Аng II type 1 receptor antagonist) microinjected into the hippocampal CA1 area on the anxiety-like behavior in rats with a model of depression. METHODS: The bilateral olfactory bulbectomy (OBX) was used as a model of depression. The stereotaxic technique was used for bilaterally (right and left) implantation of guide cannulas into CA1 hippocampal area of the OBX rats. The anxiety state of OBX rats was studied using the elevated plus-maze test. RESULTS: Тhe bilateral infusion of Ang II (0.5μg) did not change the anxiety-like behavior of OBX rats, while losartan (100μg) showed an anxiolytic-like behavior, by increasing the number and time of open arms entries, the ratio of open/total entries and open/total time and decreasing the number and time of closed arm entries. CONCLUSIONS: These findings demonstrated that the inhibition of hippocampal AT1 receptors reduces the anxiety in OBX rats, which indicates involvement of AT1 receptors in the mechanisms of OBX-induced anxiety.
BACKGROUND: Accumulated evidence suggests that the enhanced brain angiotensin II (Ang II) activity is associated with stress and anxiety. More recent reports demonstrated that Ang II function is elevated in depression, but the role of hippocampal Ang II and its receptors in this state is not well established. The present study investigated the effects of Ang II and losartan (a selective Аng II type 1 receptor antagonist) microinjected into the hippocampal CA1 area on the anxiety-like behavior in rats with a model of depression. METHODS: The bilateral olfactory bulbectomy (OBX) was used as a model of depression. The stereotaxic technique was used for bilaterally (right and left) implantation of guide cannulas into CA1 hippocampal area of the OBX rats. The anxiety state of OBX rats was studied using the elevated plus-maze test. RESULTS: Тhe bilateral infusion of Ang II (0.5μg) did not change the anxiety-like behavior of OBX rats, while losartan (100μg) showed an anxiolytic-like behavior, by increasing the number and time of open arms entries, the ratio of open/total entries and open/total time and decreasing the number and time of closed arm entries. CONCLUSIONS: These findings demonstrated that the inhibition of hippocampal AT1 receptors reduces the anxiety in OBX rats, which indicates involvement of AT1 receptors in the mechanisms of OBX-induced anxiety.
Authors: Wael Eldahshan; Mohammed A Sayed; Mohamed E Awad; Heba A Ahmed; Ellen Gillis; Waleed Althomali; Bindu Pillai; Abdulkarim Alshammari; Ladonya Jackson; Guangkuo Dong; Jennifer C Sullivan; Marion A Cooley; Mohammed Elsalanty; Adviye Ergul; Susan C Fagan Journal: Vascul Pharmacol Date: 2021-09-01 Impact factor: 5.773