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

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          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.

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          Most cited references32

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          Forced swimming test in mice: a review of antidepressant activity.

          Among all animal models, the forced swimming test (FST) remains one of the most used tools for screening antidepressants. This paper reviews some of the main aspects of the FST in mice. Most of the sensitivity and variability factors that were assessed on the FST are summarized. We have summarized data found in the literature of antidepressant effects on the FST in mice. From this data set, we have extrapolated information on baseline levels of strain, and sensitivity against antidepressants. We have shown that many parameters have to be considered in this test to gain good reliability. Moreover, there was a fundamental inter-strain difference of response in the FST. The FST is a good screening tool with good reliability and predictive validity. Strain is one of the most important parameters to consider. Swiss and NMRI mice can be used to discriminate the mechanisms of action of drugs. CD-1 seems to be the most useful strain for screening purposes, but this needs to be confirmed with some spontaneous locomotor activity studies.
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            Stress-induced hyperalgesia.

            The importance of the modulation of pain by emotion is now widely recognised. In particular, stress and anxiety, depending on their nature, duration and intensity, can exert potent, but complex, modulatory influences typified by either a reduction or exacerbation of the pain state. Exposure to either acute or chronic stress can increase pain responding under experimental conditions and exacerbate clinical pain disorders. There is evidence that exposure to chronic or repeated stress can produce maladaptive neurobiological changes in pathways associated with pain processing, resulting in stress-induced hyperalgesia (SIH). Preclinical studies of SIH are essential for our understanding of the mechanisms underpinning stress-related pain syndromes and for the identification of neural pathways and substrates, and the development of novel therapeutic agents for their clinical management. In this review, we describe clinical and pre-clinical models used to study SIH and discuss the neural substrates, neurotransmitters and neuromodulatory systems involved in this phenomenon.
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              Disruption of social bonds induces behavioral and physiological dysregulation in male and female prairie voles.

              The social disruption of losing a partner may have particularly strong adverse effects on psychological and physiological functioning. More specifically, social stressors may play a mediating role in the association between mood disorders and cardiovascular dysfunction. This study investigated the hypothesis that the disruption of established social bonds between male and female prairie voles would produce depressive behaviors and cardiac dysregulation, coupled with endocrine and autonomic nervous system dysfunction. In Experiment 1, behaviors related to depression, cardiac function, and autonomic nervous system regulation were monitored in male prairie voles during social bonding with a female partner, social isolation from the bonded partner, and a behavioral stressor. Social isolation produced depressive behaviors, increased heart rate, heart rhythm dysregulation, and autonomic imbalance characterized by increased sympathetic and decreased parasympathetic drive to the heart. In Experiment 2, behaviors related to depression and endocrine function were measured following social bonding and social isolation in both male and female prairie voles. Social isolation produced similar levels of depressive behaviors in both sexes, as well as significant elevations of adrenocorticotropic hormone and corticosterone. These alterations in behavioral and physiological functioning provide insight into the mechanisms by which social stressors negatively influence emotional and cardiovascular health in humans. © 2013.
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                Author and article information

                Journal
                Iran J Basic Med Sci
                Iran J Basic Med Sci
                ijbms
                Iranian Journal of Basic Medical Sciences
                Mashhad University of Medical Sciences (Mashhad, Iran )
                2008-3866
                2008-3874
                August 2018
                : 21
                : 8
                : 856-862
                Affiliations
                [1 ]Intracellular Recording Lab, Kerman Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran
                [2 ]Social Determinants of Health Research Center, Guilan University of Medical Sciences, Rasht, Iran
                [3 ]Health Science Research Center, Addiction Institute, Mazandaran University of Medical Sciences, Sari, Iran
                Author notes
                [* ]Corresponding author: Mohammad Shabani. Intracellular Recording Lab, Kerman Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran. Email: shabanimoh@yahoo.com; shabani@kmu.ac.ir
                Article
                10.22038/IJBMS.2018.27113.6632
                6118077
                d073f868-46d1-473c-bb12-f0e66a3895df
                © Iranian Journal of Basic Medical Sciences

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License, ( http://creativecommons.org/licenses/by/3.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 23 October 2017
                : 6 March 2018
                Categories
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