Coping with Chronic Social Stress in Mice: Hypothalamic-Pituitary-Adrenal/ Sympathetic-Adrenal-Medullary Axis Activity, Behavioral Changes and Effects of Antalarmin Treatment: Implications for the Study of Stress-Related Psychopathologies

Abstract

The aim of this study was to analyze the individual differences that lead to the development of psychopathological changes in response to chronic social stress. We also assessed the ability of an antagonist of the corticotrophin-releasing hormone (CRH) receptors to reverse the effects of stress. Male adult mice were exposed to repeated defeat experiences for 21 days using a sensorial contact model. After 18 days of defeat, two groups of subjects were established (active and passive), according to their behaviors during social confrontation. Antalarmin treatment was given for 4 and 6 days. The results corroborated previous data indicating that subjects who adopted a passive coping strategy had higher corticosterone levels after 21 days of defeat and decreased resting levels 3 days later. Moreover, they showed higher resting expression levels of hypothalamic CRH than their active counterparts. On day 24, the experimental animals were subjected to another social defeat to determine whether the stress response remained. The increase in corticosterone and hypothalamic CRH levels was similar for all of the stressed subjects, but the passive subjects also had a greater CRH response in the amygdala. Passive subjects had decreased levels of adrenal dopamine β-hydroxylase, tyrosine hydroxylase and plasma adrenaline compared to the active subjects, and lower plasma noradrenaline levels than manipulated controls. The passive profile of physiological changes in both the hypothalamic-pituitary-adrenal and sympathetic-adrenal-medullary (SAM) axes has been associated with changes related to mood disorders, such as posttraumatic stress disorder and depression. The active coping profile is characterized by similar corticosterone resting levels to controls and increased SAM activity. Both profiles showed alterations in the novel palatable and forced swimming tests, with the passive profile being the most vulnerable to the effects of stress in this last test. Pharmacological treatment with antalarmin failed to reverse the effects of stress.

Mouse social stress induces increased fear conditioning, helplessness and fatigue to physical challenge together with markers of altered immune and dopamine function

“…Despite adrenal hypertrophy, basal plasma CORT levels in blood samples collected at the termination of Expt A were not increased in CSD mice. Previous CSD studies report that basal plasma CORT is increased (Perez-Tejada et al, 2013) or unchanged (Krishnan et al, 2007). Furthermore, in faecal boli collected across the 3-day paradigm in Expt A, CORT metabolite was increased on post-stress days in CON but not in CSD mice.…”

Neuroinflammation at the interface of depression and cardiovascular disease: Evidence from rodent models of social stress

“…We and others have demonstrated the utility of the resident-intruder paradigm to study the differential consequences associated with the emergence of active and passive coping responses in the context of repeated social defeat exposure (Korte et al., 1992, Fokkema et al., 1995, Gomez-Lazaro et al., 2011, Wood et al., 2012, Chaijale et al., 2013, Perez-Tejada et al., 2013, Reyes et al., 2015, Wood et al., 2015). Analysis of behavior exhibited during defeat, such as immobility and exploration (De Miguel et al., 2011, Gomez-Lazaro et al., 2011, Perez-Tejada et al., 2013) or duration of upright posture and the latency to exhibit a supine posture signaling defeat (Wood et al., 2012, Wood et al., 2015, Reyes et al., 2015, Wood et al., 2015) can be used to statistically separate animals into passive or active subpopulations.…”

“…We and others have demonstrated the utility of the resident-intruder paradigm to study the differential consequences associated with the emergence of active and passive coping responses in the context of repeated social defeat exposure (Korte et al., 1992, Fokkema et al., 1995, Gomez-Lazaro et al., 2011, Wood et al., 2012, Chaijale et al., 2013, Perez-Tejada et al., 2013, Reyes et al., 2015, Wood et al., 2015). Analysis of behavior exhibited during defeat, such as immobility and exploration (De Miguel et al., 2011, Gomez-Lazaro et al., 2011, Perez-Tejada et al., 2013) or duration of upright posture and the latency to exhibit a supine posture signaling defeat (Wood et al., 2012, Wood et al., 2015, Reyes et al., 2015, Wood et al., 2015) can be used to statistically separate animals into passive or active subpopulations. Specifically, passive coping rodents are characterized by high levels of immobility, reduced exploratory behavior, little time spent in upright postures, and a short latency to display supine postures in response to an attack by the resident (De Miguel et al., 2011, Gomez-Lazaro et al., 2011, Wood et al., 2012, Perez-Tejada et al., 2013, Reyes et al., 2015, Wood et al., 2015), which is associated with the development of depressive-like behavioral endpoints as evidenced by increased immobility in the forced swim test (Wood et al., 2010, Gomez-Lazaro et al., 2011, Perez-Tejada et al., 2013) and reductions in sucrose preference (Wood et al., 2015).…”

The Impact of Stress on Immunity, Mechanism and Pathways Involved

“…The inflection of immune feedback by the central nervous system is resolved by a complicated system of signals that perform dual directional link between immunity, nervous and endocrine system. [8] The immune functions which are associated with the stress can be altered by many pathways, for example; SAM pathway and HPA Axis pathway. [1 2 9] The catecholamine and cortisol [10] are the products of SAM and HPA pathways which are produced by the receptors exhibited by granulocytes, lymphocytes, macrophages as well as monocytes.…”

“…[1 2 9] The catecholamine and cortisol [10] are the products of SAM and HPA pathways which are produced by the receptors exhibited by granulocytes, lymphocytes, macrophages as well as monocytes. [6,8,10,11] The hormones which link with the HPA and SAM Axis, for that immune cells have more than one or one receptors and that are called stressor hormones and these hormones either bind directly or indirectly to the surface of cell and effect the cytokine production, such as IL1,IL2,IL6,INFγ, TNF, [12,13] and immune response might [14] be affected by the stressors through many pathways. [12,15,16] Immunosenescence, [17,18] and prolonged stress can cause the abnormalities in endocrine and immune system [19] that is associated with different kinds of pathological conditions such as asthma, development of HIV and AIDS [20,21] diabetes, cancer, osteoporosis, infectious disease, auto-immune responses and Alzheimer's disease.…”