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Enhancement of the hypothalamic-pituitary-adrenal axis but not cytokine responses to stress challenges imposed during withdrawal from acute alcohol exposure in Sprague-Dawley rats.

ABSTRACT: Alcohol withdrawal is associated with reduced activity, increased anxiety, and other signs of distress.The goal of the current studies was to determine whether acute ethanol exposure would alter hypothalamic-pituitary-adrenal (HPA) axis reactivity and cytokine responses to stress challenges imposed during the withdrawal period.Male Sprague-Dawley rats were intubated with 4 g/kg of ethanol to simulate acute binge-like ethanol intake. After characterizing the blood ethanol concentrations (BECs; Experiment 1), exploratory activity in a novel environment was explored at 10, 14 and 18 h after ethanol (Experiment 2) to characterize altered activity patterns indicative of withdrawal. In Experiment 3, rats were exposed to footshock during withdrawal to examine whether prior ethanol exposure would alter cytokine and HPA axis responses to stress. Experiments 4 and 5 investigated HPA axis sensitivity and gene expression changes during restraint imposed during withdrawal.Prior ethanol exposure produced a period of stress hyper-reactivity evidenced by an enhanced HPA axis response (increased corticosterone and adrenocorticotropic hormone) observed during withdrawal. While this hyper-reactivity in response to two different stress challenges (novel environment and restraint) was accompanied by profound behavioral changes indicative of withdrawal, no alterations in cytokine changes evoked by stress were observed.Taken together, these findings provide support for the hypothesis that alcohol withdrawal enhances HPA axis reactivity to stress challenges, though not likely as the result of heightened inflammatory signaling, and may have implications for understanding the mechanisms by which stress impacts relapse drinking in humans.

SUBMITTER: Buck HM

PROVIDER: S-EPMC3192240 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Enhancement of the hypothalamic-pituitary-adrenal axis but not cytokine responses to stress challenges imposed during withdrawal from acute alcohol exposure in Sprague-Dawley rats.

Buck Hollin M HM Hueston Cara M CM Bishop Christopher C Deak Terrence T

Psychopharmacology 20110707 1

<h4>Rationale</h4>Alcohol withdrawal is associated with reduced activity, increased anxiety, and other signs of distress.<h4>Objective</h4>The goal of the current studies was to determine whether acute ethanol exposure would alter hypothalamic-pituitary-adrenal (HPA) axis reactivity and cytokine responses to stress challenges imposed during the withdrawal period.<h4>Methods</h4>Male Sprague-Dawley rats were intubated with 4 g/kg of ethanol to simulate acute binge-like ethanol intake. After chara ...[more]

PMID: 21735074

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Project description:Adolescent alcohol use comprises a significant public health concern and is often characterized by binge-like consumption patterns. While ethanol exposure in adulthood has been shown to alter the stress response, including the Hypothalamic-Pituitary-Adrenal (HPA) axis, few studies have examined whether binge-like ethanol exposure during adolescence results in enduring changes in HPA axis sensitivity in adulthood. In the present studies, adolescent Sprague-Dawley rats were given intragastric (i.g.) intubations of ethanol (4 g/kg) or vehicle once per day for three consecutive days, beginning on postnatal day (P) 30 (±1). This exposure was followed by a 2-day period of rest/withdrawal. Rats received a total of either two (Experiments 1, 2 and 3) or four (Experiment 4) cycles of ethanol exposure and were subsequently allowed to age normally until adulthood. In Experiment 1, adult, (P71-75), ethanol- or vehicle-exposed rats received a 60 min restraint stress challenge. In Experiment 2, rats received a 50 ?g/kg injection of lipopolysaccharide (LPS). In Experiment 3, rats received a challenge of 2.5 g/kg ethanol (intraperitoneally; i.p.). In Experiment 4, male and female ethanol- or vehicle- exposed rats received a 50 ?g/kg injection of LPS. In all experiments, blood samples were collected for later assessment of corticosterone (CORT), blood ethanol concentrations (BECs), and the cellular fraction of blood was analyzed for cytokine gene expression. As expected, all three challenges led to a time-dependent surge in CORT. Gene expression analyses of cytokines (Interleukin [IL]-6, IL-1?, and Tumor necrosis factor alpha [TNF?]) from the cellular fraction of blood revealed unique, time-dependent patterns of cytokine expression depending upon the nature of the adult challenge incurred (restraint, LPS, or EtOH). Importantly, adolescent ethanol exposure led to attenuated restraint and LPS-induced cytokine expression in males, whereas female rats displayed an absence of cytokine alterations, and a tendency toward heightened HPA axis reactivity. These findings suggest that adolescent ethanol exposure may cause lasting alterations in cytokine regulation and HPA axis sensitivity that (a) persist into adulthood; (b) may vary depending on the nature of the challenge incurred during adulthood; and that

Dataset Information

Enhancement of the hypothalamic-pituitary-adrenal axis but not cytokine responses to stress challenges imposed during withdrawal from acute alcohol exposure in Sprague-Dawley rats.

Publications

Enhancement of the hypothalamic-pituitary-adrenal axis but not cytokine responses to stress challenges imposed during withdrawal from acute alcohol exposure in Sprague-Dawley rats.

Similar Datasets

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