Pagliassotti. Saturated fatty acids induce endoplasmic reticulum stress and apoptosis independently of ceramide in liver cells.

The present study investigated the role of mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) in the expression of habituation of the hypothalamic-pituitary-adrenal (HPA) axis response to stress. Male rats were restrained for 1 h per day for six consecutive days. On day 6, 1 h prior to restraint stress, both restraint-naive and repeatedly restrained rats were injected s.c. with either vehicle (propylene glycol) or one of three corticosteroid receptor antagonist treatments: selective MR antagonist (RU28318 or spironolactone), selective GR antagonist (RU40555), or both MR and GR antagonists combined (RU28318+RU40555). Blood samples were collected for corticosterone measurement at the beginning of stress, during stress, and 1 h after stress termination. Repeated restraint stress produced signi®cant habituation of corticosterone responses. Acute treatment with the combined MR and GR antagonists prevented the expression of habituation. When tested alone, the MR antagonist also blocked the expression of corticosterone-response habituation, whereas the GR antagonist had no effect. Neither the MR, nor the GR antagonists alone, signi®cantly altered the corticosterone response to restraint in rats exposed to restraint for the ®rst time. The ®nal experiment examined the corticosterone response to a corticotropin releasing hormone (CRH, 3 mg/kg i.p.) challenge. Neither previous exposure to restraint or acute pretreatment with the combined MR and GR antagonists (RU28318+RU40555) altered the corticosterone response to CRH challenge. This result indicates that the expression of habituation and its blockade by corticosteroid receptor antagonists is not a result of altered pituitary-adrenal response to CRH. Overall, this study suggests that MR plays an important role in constraining the HPA axis response to restraint stress in restraint-habituated rats. The dependence of the HPA axis on MR-mediated corticosteroid negative feedback during acute stress may be an important mechanism that helps maximize the expression of stress habituation and thereby minimize exposure of target tissues to corticosteroids in the context of repeated stress.Repeated exposure to stress often leads to adaptation within stress response systems that is evident by a change in the magnitude of subsequent elicited stress responses. In some cases, repeated stress leads to an enhanced or sensitized stress response and in other cases it leads to a blunted or habituated stress response (1, 2). Although some of the conditions that lead to stress response sensitization or habituation have been characterized, there is very little understanding of the mechanisms responsible for this adaptation. We have studied a stress habituation paradigm in which rats were repeatedly exposed to restraint stress. Our studies focused on the hypothalamic-pituitary-adrenal (HPA) axis as a stress response system by which to monitor the habituation process (3, 4). For the studies reported here, we considered the possibility that corticosterone negative feedback p...

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The stressful quality of an experience, as perceived by rats, is believed to be largely represented by the magnitude of a hypothalamic-pituitary-adrenal (HPA) axis response. The hippocampus may be especially important for assessing the stressfulness of psychological stressors such as novel experience. If such is the case then experience-dependent immediate-early gene expression levels within the hippocampus may parallel relative levels of HPA axis activity. We examined this prospect in rats that were placed in four different novel environments (empty housing tub, circular arena, elevated pedestal or restraint tube). Restraint and pedestal produced the largest magnitude of increased ACTH and corticosterone secretion, arena an intermediate level (Experiment 2) and tub the least magnitude of increase. We saw a very similar experience-dependent pattern of relative Fos protein, c-fos mRNA and zif268 mRNA expression in the paraventricular nucleus of the hypothalamus. However, in hippocampus (and select regions of cortex), immediate-early gene expression was associated with the exploratory potential of the novel experience rather than level of HPA axis activity; pedestal and arena elicited the greatest immediate-early gene expression, tub an intermediate level and restraint the least amount of expression. We conclude that the stressfulness of psychological stressors is not represented by the amount of immediate-early gene induction elicited in hippocampus and cortex, nor does there appear to be a general enhancing or depressive influence of acute stress on immediate-early gene induction in those brain regions.