Aspirin pretreatment reduces ethanol withdrawal severity in a mouse model of binge drinking

Hale, Robert L.; Randall, Carrie L.; Becker, Howard C.; Turner, Katrina

doi:10.1016/0091-3057(92)90499-6

Cited by 7 publications

(6 citation statements)

References 24 publications

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“…There are many other possible explanations for this outcome, however, the first being that neither COX nor IL-1 mechanisms are involved in the behavioral changes observed in this model. Indeed, there is prior evidence to suggest that, while inhibition of prostaglandin synthesis can reverse some illness- (Avitsur et al, 1999; Bluthe et al, 1992a; De La Garza et al, 2004) and withdrawal-related (Dhir et al, 2005; Hale et al, 1992; Kaivola et al, 1983; Romeo et al, 2000) behaviors, these effects are not always observed (e.g., (Nadjar et al, 2010; Otterness et al, 1991; Segarnick et al, 1985). …”

Section: Discussionmentioning

confidence: 99%

“…Administration of drugs that inhibit prostaglandin synthesis, such as indomethacin (a nonselective COX inhibitor), have been shown to reverse the sickness response induced by injection of inflammatory compounds including LPS (de Paiva et al, 2010; Fishkin and Winslow, 1997; Yirmiya et al, 1997). Furthermore, previous studies have reported that some of the behavioral aspects of ethanol withdrawal can by prevented by prostaglandin inhibition (Dhir et al, 2005; Hale et al, 1992; Kaivola et al, 1983; Romeo et al, 2000). The goal of Experiment 5, therefore, was to determine if disruption of prostaglandin synthesis would attenuate reductions in exploratory activity and social investigation seen 18 hr after an ethanol bolus.…”

Section: Experiments 5: Effects Of Indomethacin On Withdrawal-relatmentioning

confidence: 99%

“…Prostaglandins are a final common mediator of sickness behaviors, being both the cause and consequence of cytokine induction (Dantzer, 2004; Konsman et al, 2002). Studies have shown that plasma prostaglandins are increased during acute ethanol withdrawal (Kaivola et al, 1983; Parantainen, 1983), and there is limited evidence to suggest that nonsteroidal anti-inflammatory drugs (NSAIDS) may in some instances (Dhir et al, 2005; Hale et al, 1992; Kaivola et al, 1983; Romeo et al, 2000), but not all (e.g., Segarnick et al, 1985), attenuate the negative behavioral alterations of withdrawal.…”

Section: Introductionmentioning

confidence: 99%

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Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

Richey

Doremus-Fitzwater

Buck

et al. 2012

Pharmacology Biochemistry and Behavior

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Exposure to an immunogen results in a constellation of behavioral changes collectively referred to as “sickness behaviors,” with alterations in cytokine expression previously shown to contribute to this sickness response. Since behaviors observed during ethanol withdrawal are strikingly similar to sickness behaviors, we hypothesized that behavioral manifestations of ethanol withdrawal might be an expression of sickness behaviors induced by ethanol-related changes in peripheral and/or central cytokine expression. Accordingly, behaviors exhibited during a modified social investigation test were first characterized in male rats following an acute injection of lipopolysaccharide (LPS; 100 μg/kg). Subsequently, behavioral changes after either a high (4-g/kg; Experiment 2) or low dose (0.5 g/kg; Experiment 3) of ethanol were also examined in the same social investigation test, as well as in the forced-swim test (FST; Experiment 4). Results from these experiments demonstrated similar reductions in both exploration and social investigatory behavior during acute illness and ethanol withdrawal, while a seemingly paradoxical decrease in immobility was observed in the FST during acute ethanol withdrawal. In follow-up studies, neither indomethacin (Experiment 5) nor interleukin-1 receptor antagonist (Experiment 6) pre-exposure reversed the ethanol withdrawal-induced behavioral changes observed in this social investigation test. Taken together, these studies demonstrate that the behavioral sequelae of acute illness and ethanol withdrawal are similar in nature, while antagonist studies suggest that these behavioral alterations are not reversed by blockade of IL-1 receptors or inhibition of prostaglandin synthesis. Though a direct mechanistic link between cytokines and the expression of acute ethanol withdrawal-related behaviors has yet to be found, future studies examining the involvement of brain cytokines as potential mediators of ethanol effects are greatly needed.

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Section: Discussionmentioning

confidence: 99%

Section: Experiments 5: Effects Of Indomethacin On Withdrawal-relatmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

Richey

Doremus-Fitzwater

Buck

et al. 2012

Pharmacology Biochemistry and Behavior

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“…The ethanol treatment procedure was adopted from that reported by Hale et al [18] for a multiple-exposure binge drinking model. At the ethanol dose of 4 g/kg administered by gavage, the mice appeared sedated with a marked decrease in locomotor activities, but no loss of righting reflex.…”

Section: Discussionmentioning

confidence: 99%

“…One striking feature of those studies is that the experimental animals were exposed to very high doses of ethanol. We, therefore, undertake to investigate the effects on PBBS in a mouse model of binge drinking using a relatively low dose of ethanol [18].…”

Section: Introductionmentioning

confidence: 99%

Effects of Ethanol on Peripheral Benzodiazepine Binding Sites in the Mouse Cerebellum and Brain Stem

Wong

Tan²,

Kwan³

et al. 1995

Pharmacology

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[³H]PK 11195 binding to the peripheral benzodiazepine binding site was investigated in the brain and liver of mice treated with ethanol (4 g/kg, p.o.) daily for 5 days. In the brain stem, B_max was decreased by 78% in the ethanol-treated group with unaltered K_d (2 nM). The ethanol-withdrawn group did not differ from the control group in both parameters. In the cerebellum, B_max was decreased by 74% but the binding affinity increased 5-fold as the K_d decreased from 10 to 2 nM. The ethanol-withdrawn group did not differ significantly from the ethanol-treated group. No changes were observed in the cerebrum and liver. These results further support the idea that [³H]PK 11195 binding may be a useful marker for ethanol consumption. The observed changes in these binding sites may represent a functional adaptive response to the ethanol insult and/or a role in the mediation of the effects of ethanol.

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Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons

Bekdash

Harrison

2015

Brain and Behavior

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BackgroundAlcohol abuse and dependence are a serious public health problem. A large number of alcohol-regulated genes, (ARGs) are known to be influenced by alcohol use and withdrawal (AW), and recent evidence suggests that neuroadaptation to alcohol may be due in part to epigenetic changes in the expression of ARGs. Gabra4, which encodes the α4 subunit of GABAA receptors (GABAARs), is one of a number of ARGs that show remarkable plasticity in response to alcohol, being rapidly upregulated by acute alcohol exposure. This study addressed the effects of AW on changes in the expression of Gabra4 and related genes that encode other subunits of GABAARs, and the potential regulation of Gabra4 by microRNAs.MethodsWe studied gene and microRNAs expression, using RT-PCR and microRNA microarray in cultured cortical neurons treated with alcohol, which was then removed in order to simulate AW in vitro. We also used microRNA mimics or inhibitors, and a promoter-reporter construct carrying the 3′UTR of Gabra4.ResultsEleven hours after removal of alcohol, Gabra4 was downregulated, with a modest increase in the expression of Gabrg2, but no change in the expression of Gabra1, Gabrd, or Gabrb2. microRNA profiling in neurons undergoing AW revealed upregulation in the expression of miR-155, miR-186, miR-24, and miR-375 after 8 h of AW. Transfection with molecular mimics of miR-186, miR-24, or miR-375 also downregulated Gabra4 expression, whereas transfection with the corresponding inhibitors of these microRNAs normalized Gabra4 expression in AW neurons to the level measured in control neurons. Promoter-reporter experiments supported the idea that miR-155, miR-186, miR-24, miR-27b, or miR-375 bind to the 3′UTR of Gabra4 and thereby inhibit protein production.ConclusionsOur data suggest that AW decreases Gabra4 expression, and that this may be mediated in part by the induction of specific microRNAs in cortical neurons during AW.

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Aspirin pretreatment reduces ethanol withdrawal severity in a mouse model of binge drinking

Cited by 7 publications

References 24 publications

Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

Acute illness-induced behavioral alterations are similar to those observed during withdrawal from acute alcohol exposure

Effects of Ethanol on Peripheral Benzodiazepine Binding Sites in the Mouse Cerebellum and Brain Stem

Downregulation of Gabra4 expression during alcohol withdrawal is mediated by specific microRNAs in cultured mouse cortical neurons

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