Abstract
In the present study, we evaluate the effect of acute restraint stress (15 min) of male Wistar rats on social interaction measurements and c-Fos immunoreactivity (c-Fos-ir) expression, a marker of neuronal activity, in areas involved with the modulation of acute physical restraint in rats, i.e., the paraventricular nucleus of the hypothalamus (PVN), median raphe nucleus (MnR), medial prefrontal cortex (mPFC), cingulate prefrontal cortex (cPFC), nucleus accumbens (NaC), hippocampus (CA3), lateral septum (LS) and medial amygdala (MeA). We considered the hypothesis that restraint stress exposure could promote social withdrawal induced by the activation of the hypothalamic-pituitary-adrenocortical (HPA) axis, and increase c-Fos expression in these limbic forebrain areas investigated. In addition, we investigated whether pretreatment with the atypical antipsychotic clozapine (5 mg/kg; I.P.) could attenuate or block the effects of restraint on these responses. We found that restraint stress induced social withdrawal, and increased c-Fos-ir in these areas, demonstrating that a single 15 min session of physical restraint of rats effectively activated the HPA axis, representing an effective tool for the investigation of neuronal activity in brain regions sensitive to stress. Conversely, pretreatment with clozapine, prevented social withdrawal and reduced c-Fos expression. We suggest that treatment with clozapine exerted a preventive effect in the social interaction deficit, at least in part, by blocking the effect of restraint stress in brain regions that are known to regulate the HPA-axis, including the cerebral cortex, hippocampus, hypothalamus, septum and amygdala. Further experiments will be done to confirm this hypothesis.
Highlights
Stress is a natural biological response that enables individuals to cope with environmental stressors
The results demonstrated that forced swim stress (FSS) produced a significant elevation of inducible early genes (IEGs) transcription in different brain regions while the response of blonanserin-treated rats to FSS showed that the upregulation of IEGs was greatly reduced in the striatum, but was preserved in the prefrontal cortex and the ventral hippocampus
The aim of this study was to assess the effect of acute restraint stress (15 min) in social behavior, and c-Fos immunoreactivity in areas associated with the stress response, such as hypothalamus, median raphe nucleus, prefrontal cortex, nucleus accumbens, hippocampus, septum and amygdala
Summary
Stress is a natural biological response that enables individuals to cope with environmental stressors. The stress response activates the autonomic nervous system and the hypothalamicpituitary-adrenocortical (HPA) axis [1]. The deriving increase in catecholamines and glucocorticoids triggers proper behavioral and physiological reactions [1, 2] that depend on the type, intensity and time of exposure to the stressor stimulus [3]. Being a reaction aimed to guarantee survival, exposition to stressful events is associated to an increased risk to develop stress-related psychopathology [4, 5]. Exposure of rodents to different stress paradigms induces behavioral and physiological changes [6–8]. Physical restraint is considered a very effective sort of inescapable stress [9]. It results from the aversive nature of remaining immobile and induces increases in adrenocorticotropic hormone and corticosterone [9]
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