Effects of acute versus chronic social and non-social stress on social fear conditioning and the regulatory role of neuropeptides in male mice

Abstract

Stress is a situation common in life and demands physiological and behavioral changes to reestablish homeostatic equilibrium. Stressor exposure may cause stressor-dependent responses including behavioral and neuroendocrine responses as activation of the HPA axis and the oxytocin (OXT) system. OXT secretion into the blood has been observed in response to acute psychological and social stressors such as restraint and social defeat-situations accompanied by increased anxiety-related behavior and social avoidance, respectively. The brain OXT system is best known for its anxiolytic, stress-protective and pro-social actions and can, thus, be important in coping with non-social and social stress as well as anxiety, social avoidance and social fear. The behavioral effects of OXT in the context of social fear have been extensively studied in an animal model of social fear, i.e. social fear conditioning (SFC), that reproduces characteristics that are displayed by patients with social anxiety disorder. However, the impact of the related neuropeptides as OXT and vasopressin (AVP) has not been studied in the context of SFC despite its substantial involvement in the regulation of anxiety. Based on these findings, I aim to investigate, whether (i) restraint and social defeat stress increases the vulnerability to SFC and may impair social fear extinction, and (ii) to extent the impact of stress on SFC using chronic restraint stress for 2 weeks or 3 weeks exposure to chronic subordinate colony housing. (iii) Next, investigate if intracerebral OXT can reverse, while AVP is able to strengthen, the stress-protocols effects on SFC acquisition and/or extinction. Furthermore, I aim to evaluate alterations in the oxytocinergic and vasopressinergic neuronal network involved in the interaction of stress and SFC. To this, other sets of animals will be treated with either OXT or AVP (intracerebroventricular; icv) prior to SFC extinction training, and social fear extinction behavior and neuroendocrine parameters (ACTH, corticosterone, OXT, AVP) will be analyzed. Also, the expression of brain OXT and AVP receptors will be evaluated by receptor binding autoradiography.