Effects of chronic alcohol consumption and withdrawal on the response of the male and female hypothalamic-pituitary-adrenal axis to acute immune stress.

Department of Anatomy, Faculty of Medicine, University of Porto, Alameda Professor HernĂ¢ni Monteiro, 4200-319 Porto, Portugal.
Brain research (Impact Factor: 2.46). 03/2012; 1444:27-37. DOI: 10.1016/j.brainres.2012.01.013
Source: PubMed

ABSTRACT The hypothalamic-pituitary-adrenal (HPA) axis plays a central role in the response to stress, and its activity is sexually dimorphic and modulated by sex steroids. Recent work indicates that HPA axis functioning is disturbed by chronic alcohol consumption and subsequent withdrawal in rats of both sexes, but particularly in females. To examine the influence of sex steroid hormones in HPA axis response to acute stress after ingestion of a 20% ethanol solution over 6months and subsequent withdrawal (2months), intact males, and estradiol- and oil-injected ovariectomized females received a single intraperitoneal injection of lipopolysaccharide (LPS). Six hours after LPS administration, corticosterone concentrations were increased in all male groups; however, in ethanol-treated rats they remained below those of control and withdrawn rats. mRNA levels of corticotrophin-releasing hormone (CRH) increased, and were identical in all groups after LPS stimulation, whereas those of vasopressin, although increased, remained below control levels. LPS stimulation elevated corticosterone concentrations in all oil-injected female groups, but did not alter those of estradiol-injected females. In oil- and estradiol-injected ethanol-treated females, CRH mRNA levels did not change in response to LPS stimulation, whereas those of vasopressin increased, but stayed below control levels. In withdrawn oil- and estradiol-injected females, CRH and vasopressin gene expression increased, but did not reach control levels. These data show that prolonged alcohol consumption produces long-lasting, possibly irreversible, changes in the neuroendocrine system that regulates the production of corticosteroids, and that these consequences are more profound in females, particularly when estrogen levels are low.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Exposure to alcohol during adolescence exerts long-term effects on the adult brain stress circuits, causing many changes that persist into adulthood. Here we examined the consequences of adolescent intermittent ethanol [AIE, administered from postnatal day (PND) 28-42] on the hypothalamic-pituitary-adrenal (HPA) axis-related brain circuitry of rats challenged with an intragastric administration of alcohol in adulthood (PND 70-71). Both male and female adolescent rats were exposed to alcohol vapors, while controls did not receive the drug, to assess whether AIE alters adult alcohol response in a sex-specific manner. We demonstrated that AIE increased PVN Avp mRNA levels during late (PND 42) but not middle (PND 36) adolescence in males. While an alcohol challenge administered to 70-71-day-old rats increased Crf mRNA levels in males and Avp mRNA levels in females, AIE blunted both effects. These results suggest that AIE produced long-lasting changes in the responsiveness of the HPA axis to a subsequent alcohol challenge in a sex-specific manner. Furthermore, AIE altered adrenergic brain stem nuclei involved in stress responses in adulthood, resulting in increased numbers of phenylethanolamine N-methyltransferease (PNMT) neurons in male C2 and female C1 regions. This tended to enhance activation of the male C2 nucleus upon alcohol challenge. Collectively, these results suggest that AIE exerts long-term effects on the ability of the PVN to respond to an alcohol challenge in adulthood, possibly mediated by catecholaminergic input from the brain stem to the PVN.
    Neuroscience 01/2013; · 3.12 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Depression is a commonly reported co-morbidity during rehabilitation from alcohol use disorders and its presence is associated with an increased likelihood of relapse. Interventions which impede the development of depression could be of potential benefit if incorporated into treatment programs. We previously demonstrated an ameliorative effect of physical exercise on depressive behaviors in a mouse model of alcohol abstinence. Here, we show that environmental enrichment (cognitive and social stimulation) has a similar beneficial effect. The hypothalamic-pituitary-adrenal (HPA) axis is a key physiological system regulating stress responses and its dysregulation has been separably implicated in the pathophysiology of depression and addiction disorders. We performed a series of dexamethasone challenges and found that mice undergoing 2 weeks of alcohol abstinence had significantly greater corticosterone and ACTH levels following a DEX-CRH challenge compared to water controls. Environmental enrichment during alcohol abstinence corrected the abnormal DEX-CRH corticosterone response despite a further elevation of ACTH levels. Examination of gene expression revealed abstinence-associated alterations in glucocorticoid receptor (Gr), corticotrophin releasing hormone (Crh) and pro-opiomelanocortin (Pomc1) mRNA levels which were differentially modulated by environmental enrichment. Overall, our study demonstrates a benefit of environmental enrichment on alcohol abstinence-associated depressive behaviors and HPA axis dysregulation.
    Frontiers in Pharmacology 01/2013; 4:93.
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The immune response is essential for keeping an organism healthy and for defending it from different types of pathogens. It is a complex system that consists of a large number of components performing different functions. The adequate and controlled interaction between these components is necessary for a robust and strong immune response. There are, however, many factors that interfere with the way the immune response functions. Stress and ageing now consistently appear in the literature as factors that act upon the immune system in the way that is often damaging. This review focuses on the role of stress and ageing in altering the robustness of the immune response first separately, and then simultaneously, discussing the effects that emerge from their interplay. The special focus is on the psychological stress and the impact that it has at different levels, from the whole system to the individual molecules, resulting in consequences for physical health.
    Age 02/2014; · 6.28 Impact Factor