Angiotensin II type 1 receptor blocker losartan attenuates locomotor, anxiety-like behavior, and passive avoidance learning deficits in a sub-chronic stress model.

Abstract

Objective(s):Stress alters sensory and cognitive function in humans and animals. Angiotensin (AT) receptors have demonstrated well-established interactions in sets of physiological phenomena. AT1 receptors can play a part in stress-induced activation of hypothalamic-pituitary-adrenal (HPA) axis; besides angiotensinergic neurotransmission plays a pivotal role in stress-evoked physiological responses. AT1 receptors are also involved in nociception and memory. The objective of the current study was to evaluate the effects of losartan as an AT1R antagonist in locomotor activity, nociception and memory impairments induced by sub-chronic swim stress.Materials and Methods:A two-session forced swimming stress protocol was administered to the rats. Pretreatment with losartan (10 mg/kg, IP) or saline was made before each swimming session. Locomotor activity, anxiety-like behavior, nociception, and passive avoidance learning were evaluated 24 hr after last swim stress session. Results:Swim stress induced increased anxiety-like behavior in the open field test, which pretreatment with losartan did counterbalance. Increased thermal threshold was observed in the nociceptive measurement after swim stress. Pretreatment with losartan attenuated the increased threshold and also inhibited a decreased step-through latency that was observed in the memory paradigm after swim stress. Conclusion:The results of this study indicate that sub-chronic swim stress impairs passive avoidance learning, anxiety-like behaviors, and nociception; and AT1 receptor seems to have a modulatory role in these alterations. However, further studies are suggested to examine the protective effect of AT1R inhibitors on stress-induced impairments in sensory and cognitive function.