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Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors.

ABSTRACT: Alcohol dependence is linked to dysregulation of the hypothalamic-pituitary-adrenal axis. Here, we investigated effects of repeated ethanol intoxication-withdrawal cycles (using chronic intermittent ethanol vapor inhalation; CIE) and abstinence from CIE on peak and nadir plasma corticosterone (CORT) levels. Irritability- and anxiety-like behaviors as well as glucocorticoid receptors (GR) in the medial prefrontal cortex (mPFC) were assessed at various intervals (2h-28d) after cessation of CIE. Results show that peak CORT increased during CIE, transiently decreased during early abstinence (1-11d), and returned to pre-abstinence levels during protracted abstinence (17-27d). Acute withdrawal from CIE enhanced aggression- and anxiety-like behaviors. Early abstinence from CIE reduced anxiety-like behavior. mPFC-GR signaling (indexed by relative phosphorylation of GR at Ser211) was transiently decreased when measured at time points during early and protracted abstinence. Further, voluntary ethanol drinking in CIE (CIE-ED) and CIE-naïve (ED) rats, and effects of CIE-ED and ED on peak CORT levels and mPFC-GR were investigated during acute withdrawal (8h) and protracted abstinence (28d). CIE-ED and ED increased peak CORT during drinking. CIE-ED and ED decreased expression and signaling of mPFC-GR during acute withdrawal, an effect that was reversed by systemic mifepristone treatment. CIE-ED and ED demonstrate robust reinstatement of ethanol seeking during protracted abstinence and show increases in mPFC-GR expression. Collectively, the data demonstrate that acute withdrawal from CIE produces robust alterations in GR signaling, CORT and negative affect symptoms which could facilitate excessive drinking. The findings also show that CIE-ED and ED demonstrate enhanced relapse vulnerability triggered by ethanol cues and these changes are partially mediated by altered GR expression in the mPFC. Taken together, transition to alcohol dependence could be accompanied by alterations in mPFC stress-related pathways that may increase negative emotional symptoms and increase vulnerability to relapse.

SUBMITTER: Somkuwar SS

PROVIDER: S-EPMC5557646 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors.

Somkuwar Sucharita S SS Vendruscolo Leandro F LF Fannon McKenzie J MJ Schmeichel Brooke E BE Nguyen Tran Bao TB Guevara Jasmin J Sidhu Harpreet H Contet Candice C Zorrilla Eric P EP Mandyam Chitra D CD

Psychoneuroendocrinology 20170612

Alcohol dependence is linked to dysregulation of the hypothalamic-pituitary-adrenal axis. Here, we investigated effects of repeated ethanol intoxication-withdrawal cycles (using chronic intermittent ethanol vapor inhalation; CIE) and abstinence from CIE on peak and nadir plasma corticosterone (CORT) levels. Irritability- and anxiety-like behaviors as well as glucocorticoid receptors (GR) in the medial prefrontal cortex (mPFC) were assessed at various intervals (2h-28d) after cessation of CIE. Re ...[more]

PMID: 28647675

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Project description:Host responses to pathogens include defenses that reduce infection burden (i.e., resistance) and traits that reduce the fitness consequences of an infection (i.e., tolerance). Resistance and tolerance are affected by an organism's physiological status. Corticosterone ("CORT") is a hormone that is associated with the regulation of many physiological processes, including metabolism and reproduction. Because of its role in the stress response, CORT is also considered the primary vertebrate stress hormone. When secreted at high levels, CORT is generally thought to be immunosuppressive. Despite the known association between stress and disease resistance in domesticated organisms, it is unclear whether these associations are ecologically and evolutionary relevant in wildlife species. We conducted a 3x3 fully crossed experiment in which we exposed American toads (Anaxyrus [Bufo] americanus) to one of three levels of exogenous CORT (no CORT, low CORT, or high CORT) and then to either low or high doses of the pathogenic chytrid fungus Batrachochytrium dendrobatidis ("Bd") or a sham exposure treatment. We assessed Bd infection levels and tested how CORT and Bd affected toad resistance, tolerance, and mortality. Exposure to the high CORT treatment significantly elevated CORT release in toads; however, there was no difference between toads given no CORT or low CORT. Exposure to CORT and Bd each increased toad mortality, but they did not interact to affect mortality. Toads that were exposed to CORT had higher Bd resistance than toads exposed to ethanol controls/low CORT, a pattern opposite that of most studies on domesticated animals. Exposure to CORT did not affect toad tolerance to Bd. Collectively, these results show that physiological stressors can alter a host's response to a pathogen, but that the outcome might not be straightforward. Future studies that inhibit CORT secretion are needed to better our understanding of the relationship between stress physiology and disease resistance and tolerance in wild vertebrates.

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Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors.

Publications

Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors.

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