Sex differences in binge‐like EtOH drinking, corticotropin‐releasing hormone and corticosterone: effects of β‐endorphin

Nentwig, Todd B.; Wilson, Douglas; Keen-Rhinehart, Erin; Grisel, Judith E.

doi:10.1111/adb.12610

Cited by 26 publications

(38 citation statements)

References 46 publications

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“…For this reason, a comparison of 4 weeks MC model with 4 weeks LD diet potentially decreases the duration of alcohol exposure effect but increases more the differences between the amount of alcohol consumed by the mice in each model. Third of all, to increase the sensitivity of our analysis we used in our experiments only female mice as is pretty well known that the effect of alcohol is sex dependent in mice and humans 55,[60][61][62][63][64] . Actually, our ongoing current work in the lab is focused on specific cellular immune effects present only in females and not observed in male mice (data not presented, manuscript in preparation).…”

Section: Discussionmentioning

confidence: 99%

Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption

Vogle

Qian

Zhu

et al. 2020

Sci Rep

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Murine models of chronic alcohol consumption are frequently used to investigate alcoholic liver injury and define new therapeutic targets. Lieber-DeCarli diet (LD) and Meadows-Cook diet (MC) are the most accepted models of chronic alcohol consumption. It is unclear how similar these models are at the cellular, immunologic, and transcriptome levels. We investigated the common and specific pathways of LD and MC models. Livers from LD and MC mice were subjected to histologic changes, hepatic leukocyte population, hepatic transcripts level related to leukocyte recruitment, and hepatic RNA-seq analysis. Cross-species comparison was performed using the alcoholic liver disease (ALD) transcriptomic public dataset. Despite LD mice have increased liver injury and steatosis by alcohol exposure, the number of CD45 + cells were reduced. Opposite, MC mice have an increased number of monocytes/liver by alcohol. The pattern of chemokine gradient, adhesion molecules, and cytokine transcripts is highly specific for each model, not shared with advanced human alcoholic liver disease. Moreover, hepatic RNA-seq revealed a limited and restricted number of shared genes differentially changed by alcohol exposure in these 2 models. Thus, mechanisms involved in alcohol tissue injury are model-dependent at multiple levels and raise the consideration of significant pathophysiological diversity of human alcoholic liver injury. Murine models are frequently used to investigate new pathophysiological pathways of human diseases and many new treatment trials for alcoholic liver disease (ALD) are based on preclinical testing provided by murine models. ALD in humans is the result of a complex interaction between the alcoholic effects on gut microbiota, intestinal cells, immune system, and the hepatic microenvironment 1,2. Based on an extensive body of literature, alcohol increases the intestinal permeability and subsequent systemic translocation of bacterial products, e.g. LPS 1,3,4. Stimulation of Toll-like receptors (TLR) by bacterial products results in immune cell activation related to hepatic alcohol metabolic process that has a deleterious effect on the liver, resulting in histological features of ALD: steatosis, innate immune infiltrate with predominance of neutrophils and monocytes, and histological signs of hepatocyte dysfunction (Mallory hyaline formation, ballooning hepatocyte) 3,5-7. ALD includes a spectrum of histological and clinical entities: steatosis, steatohepatitis, and alcoholic hepatitis 8,9. In time, chronic liver injury with a dysregulated innate immune response results in alcohol-induced progressive hepatic fibrogenesis, liver cirrhosis and end-stage liver disease 10. Based on this classical paradigm, few trials have been attempted to control an exacerbated innate immune response or to improve hepatocyte function. Besides steroids that may be beneficial for only subsets of patients with alcoholic hepatitis 11 , no other treatments have proven consistent survival benefit 12. Moreover, treatment of anti-TNFα in alcoholic hepati...

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Section: Discussionmentioning

confidence: 99%

Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption

Vogle

Qian

Zhu

et al. 2020

Sci Rep

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“…Data from rodent studies support the notion that females exposed to alcohol will imbibe more than males and become dependent more quickly than males ( Li and Lumeng, 1984 ; Adams et al, 1991 ). Previous data from our laboratory indicate that βE is integral in the sexually dimorphic connection between stress and EtOH consumption ( Barfield et al, 2010 ; McGonigle et al, 2016 ; Nentwig et al, 2018 ). For example, βE deficient mice have enhanced stress reactivity and anxiety-like behaviors as well as a decreased ability to behaviorally manage stress ( Grisel et al, 2008 ; Barfield et al, 2010 ; McGonigle et al, 2016 ; Nentwig et al, 2018 ).…”

Section: Introductionmentioning

confidence: 86%

“…Previous data from our laboratory indicate that βE is integral in the sexually dimorphic connection between stress and EtOH consumption ( Barfield et al, 2010 ; McGonigle et al, 2016 ; Nentwig et al, 2018 ). For example, βE deficient mice have enhanced stress reactivity and anxiety-like behaviors as well as a decreased ability to behaviorally manage stress ( Grisel et al, 2008 ; Barfield et al, 2010 ; McGonigle et al, 2016 ; Nentwig et al, 2018 ). These phenotypic differences are accompanied by greater CRH expression in the hypothalamus, AMY and BNST, which is correlated with increased serum cortisol and hypertrophied adrenal glands ( McGonigle et al, 2016 ).…”

Section: Introductionmentioning

confidence: 86%

“…βE provides negative feedback to limit the duration of HPA axis activation, and it acts within the amygdala (AMY) to regulate behavioral responses to stressful stimuli and restore homeostasis ( Charmandari et al, 2005 ). Genetic conditions that result in a reduction or elimination of βE signaling lead to an overactive HPA axis and an inability to exhibit adaptive coping responses to stress ( Grisel et al, 2008 ; Barfield et al, 2010 ; McGonigle et al, 2016 ; Nentwig et al, 2018 ). In general, there is an inverse relationship between βE and anxiety-like behavior in mice ( Grisel et al, 2008 ; Barfield et al, 2010 ; Nentwig et al, 2018 ), and lack of βE induces hyperactivity of the HPA axis ( McGonigle et al, 2016 ; Nentwig et al, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

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Sex and β-Endorphin Influence the Effects of Ethanol on Limbic Gabra2 Expression in a Mouse Binge Drinking Model

et al. 2018

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Binge drinking is a widespread problem linked to increased risk for alcohol-related complications, including development of alcohol use disorders. In the last decade, binge drinking has increased significantly, specifically in women. Clinically, sexually dimorphic effects of alcohol are well-characterized, however, the underlying mechanisms for these dimorphisms in the physiological and behavioral effects of alcohol are poorly understood. Among its many effects, alcohol consumption reduces anxiety via the inhibitory neurotransmitter GABA, most likely acting upon receptors containing the α-2 subunit (Gabra2). Previous research from our laboratory indicates that female mice lacking the endogenous opioid peptide β-endorphin (βE) have an overactive stress axis and enhanced anxiety-like phenotype, coupled with increased binge-like alcohol consumption. Because βE works via GABA signaling to reduce anxiety, we sought to determine whether sexually dimorphic binge drinking behavior in βE deficient mice is coupled with differences in CNS Gabra2 expression. To test this hypothesis, we used βE knock-out mice in a “drinking in the dark” model where adult male and female C57BL/6J controls (βE +/+) and βE deficient (βE -/-; B6.129S2-Pomctm1Low/J) mice were provided with one bottle of 20% ethanol (EtOH) and one of water (EtOH drinkers) or two bottles of water (water drinkers) 3 h into the dark cycle for four consecutive days. Following a binge test on day 4, limbic tissue was collected and frozen for subsequent qRT-PCR analysis of Gabra2 mRNA expression. Water-drinking βE +/+ females expressed more Gabra2 in central nucleus of the amygdala and the bed nucleus of the stria terminalis than males, but this sex difference was absent in the βE -/- mice. Genotype alone had no effect on alcohol consumption or drug-induced increase in Gabra2 expression. In contrast, βE expression had bi-directional effects in females: in wildtypes, Gabra2 mRNA was reduced by binge EtOH consumption, while EtOH increased expression in βE -/- females to levels commensurate with drug-naïve βE +/+ females. These results support the contention that βE plays a role in sexually dimorphic binge-like EtOH consumption, perhaps through differential expression of GABAA α2 subunits in limbic structures known to play key roles in the regulation of stress and anxiety.

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“…For this experimental procedure, we followed a modification of a previously published protocol . This paradigm is a widely accepted animal model of binge‐like ethanol drinking that promotes high levels of ethanol intake.…”

Section: Methodsmentioning

confidence: 99%

Gender differences in the effects of cannabidiol on ethanol binge drinking in mice

2019

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The purpose of this study was to explore the effects of cannabidiol (CBD) on binge drinking and evaluate potential gender-related differences. To this aim, male and female C57BL/6J mice (n = 60 per sex) were exposed to the drinking in the dark (DID) model for 4 weeks (DID-1 to DID-4). Dose-response effects of CBD on the ethanol intake were tested by acute (day-4 of DID-3) or repeated administration (day-1 to 4 of DID-4) (experiment 1: CBD 15, 30, and 60 mg/kg, i.p.; experiment 2: CBD 90 mg/kg, i.p.). Finally, we analyzed the relative gene expression of tyrosine hydroxylase (TH) and μ-opioid receptor (OPRM1) and cannabinoid CB1 receptor (CB 1 r) in the ventral tegmental area (VTA) and in the nucleus accumbens (NAc), respectively, by real-time quantitative PCR. Females exhibited higher ethanol intake during each DID session. Interestingly, females also showed higher expression of TH and OPRM1, without any difference in CB 1 r. Only the acute administration of CBD at the highest dose (90 mg/kg) reduced significantly ethanol consumption in both sexes. Chronic CBD administration (30, 60 and 90 mg/kg) reduced ethanol intake in males, whereas in females a significant reduction was only achieved with the highest dose (90 mg/kg). Repeated administration with CBD (60 mg/kg) significantly reduced TH and OPRM1 in males. In addition, CBD (30 and 60 mg/kg) significantly reduced CB 1 r in males. No effect was observed in females. Taken together, these findings suggest that CBD may be of interest for treating binge-drinking patterns and that gender-related difference may affect the treatment outcome.

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Sex differences in binge‐like EtOH drinking, corticotropin‐releasing hormone and corticosterone: effects of β‐endorphin

Cited by 26 publications

References 46 publications

Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption

Restricted immunological and cellular pathways are shared by murine models of chronic alcohol consumption

Sex and β-Endorphin Influence the Effects of Ethanol on Limbic Gabra2 Expression in a Mouse Binge Drinking Model

Gender differences in the effects of cannabidiol on ethanol binge drinking in mice

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