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 Hernâni Monteiro, 4200-319 Porto, Portugal. Brain research
(Impact Factor: 2.84).
03/2012; 1444:27-37. DOI: 10.1016/j.brainres.2012.01.013
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were increased in all male groups; however, in ethanol-treated rats they remained below those of control and withdrawn rats.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 In withdrawn oil- and estradiol-injected females, CRH and vasopressin gene expression increased, but did not reach control levels.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.
Available from: Claudia E Mohn
- "different authors (Irie et al., 2008; Souza et al., 2009). The 20% alcohol consumption model used in this study has been reported in many studies (Hip olito et al., 2011; Silva and Madeira, 2012; Souza et al., 2009). Four months of alcohol ingestion was determined to guarantee a chronic condition. "
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The aim of this study was to assess the effects of chronic alcohol consumption on periodontitis development in rats.
Periodontal disease was experimentally induced by lipopolysaccharide (LPS; 2 mg/ml) injections into the gingival tissue around first upper and lower molar's neck, and into the interdental space between first and second molars. This protocol was repeated for 6 weeks on days 1, 3, and 5 of each week. Chronic alcohol consumption was induced by 20% ethanol (EtOH) as the only liquid source during 4 months.
Chronic alcohol consumption by itself increased alveolar bone loss and biological mediators of periodontal disease such as prostaglandin E2 (PGE2 ) content on gingival tissue, and inducible nitric oxide synthase activity plus PGE2 content in submandibular gland. Unexpectedly, alcohol consumption did not increase the damage evoked by the proved model of LPS injections for periodontitis induction.
Results suggest 20% alcohol consumption during 4 months generates differential effects on oral health of rats, depending on its pathophysiological state: It would exacerbate the inflammatory condition when periodontal damage is absent, but it would not when damage is installed.
Available from: Terence Y Pang
- "It is known that chronic alcohol consumption leads to prolonged activation of the HPA axis, persistent increases in circulating cortisol/corticosterone levels and culminating in dysregulation of crh gene expression which itself is a crucial factor in mediating chronic alcohol-related neuroadaptations (see review by Heilig and Koob, 2007). Our finding of decreased hypothalamic crh gene expression after protracted abstinence following chronic ethanol consumption is consistent with previous reports (Falco et al., 2009; Silva and Madeira, 2012). However, it is likely that the down-regulation of crh is a key pathological change during the process of chronic alcohol consumption which persists once alcohol is withdrawn (Richardson et al., 2008). "
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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.
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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.
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