Effects of Withdrawal from Chronic Intermittent Ethanol Exposure on Sleep Characteristics of Female and Male Mice

Huitrón‐Reséndiz, Salvador; Nadav, Tali; Krause, Stephanie; Cates-Gatto, Chelsea; Polis, Ilham; Roberts, Amanda J.

doi:10.1111/acer.13584

Cited by 23 publications

(19 citation statements)

References 68 publications

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“…We used the chronic intermittent ethanol two bottle choice (CIE-2BC) paradigm to generate ethanol dependent mice for this study (Figure 1). This method consistently produces ethanol dependence in C57BL/6J mice 35–37 , as exhibited by their increased ethanol drinking, anxiety-like behavior and reward deficits. All experiments in this study were conducted across three groups: 1) naïve mice ( n = 33) that did not receive any ethanol, 2) Non-Dep mice ( n = 40) that received only two-bottle choice to control for the vapor exposure, and 3) Dep mice ( n = 38) that received two-bottle choice and chronic-intermitent ethanol vapor exposure.…”

Section: Resultsmentioning

confidence: 97%

“…To induce ethanol dependence, we used the chronic intermittent ethanol two bottle choice (CIE-2BC) paradigm. This method consistently produces ethanol dependence in C57BL/6J mice 35–37 , as exhibited by their increased ethanol drinking, anxiety-like behavior and reward deficits. We exposed 78 mice to a limited access ethanol (15% w/v) two-bottle choice (2BC) paradigm followed by either chronic intermittent ethanol (CIE) exposure in vapor chambers (La Jolla Alcohol Research, La Jolla, CA), to induce ethanol dependence (Dep, n =38), or air exposure in identical chambers (Non-Dep, n = 40).…”

Section: Methodsmentioning

confidence: 97%

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IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

Patel

Khom

Steinman

et al. 2019

Brain, Behavior, and Immunity

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The interleukin-1 system (IL-1) is a prominent pro-inflammatory pathway responsible for the initation and regulation of immune responses. Human genetic and preclinical studies suggest a critical role for IL-1β signaling in ethanol drinking and dependence, but little is known about the effects of chronic ethanol on the IL-1 system in addiction-related brain regions such as the central amygdala (CeA). In this study, we generated naïve, non-dependent (Non-Dep) and dependent (Dep) male mice using a paradigm of chronic-intermittent ethanol vapor exposure interspersed with two-bottle choice to examine 1) the expression of IL-1β, 2) the role of the IL-1 system on GABAergic transmission, and 3) the potential interaction with the acute effects of ethanol in the CeA. Immunohistochemistry with confocal microscopy was used to assess expression of IL-1β in microglia and neurons in the CeA, and whole-cell patch clamp recordings were obtained from CeA neurons to measure the effects of IL-1β (50 ng/ml) or the endogenous IL-1 receptor antagonist (IL-1ra; 100 ng/ml) on action potential-dependent spontaneous inhibitory postsynaptic currents (sIPSCs). Overall, we found that IL-1β expression is significantly increased in microglia and neurons of Dep compared to Non-Dep and naïve mice, IL-1β and IL-1ra bi-directionally modulate GABA transmission through both pre- and postsynaptic mechanisms in all three groups, and IL-1β and IL-1ra do not alter the facilitation of GABA release induced by acute ethanol. These data suggest that while ethanol dependence induces a neuroimmune response in the CeA, as indicated by increased IL-1β expression, this does not significantly alter the neuromodulatory role of IL-1β on synaptic transmission.

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Section: Resultsmentioning

confidence: 97%

Section: Methodsmentioning

confidence: 97%

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

Patel

Khom

Steinman

et al. 2019

Brain, Behavior, and Immunity

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“…Sleep disturbances are a hallmark of AUD disorders; insomnia is commonly experienced during abstinence and may contribute to relapse [36]. In mice, 4 weeks of CIE exposure combined with 2BC reduces the quantity and quality of slow-wave sleep 4 days into withdrawal [55]. In the present study, CIE did not affect sleep parameters recorded in the CLAMS chambers (bouts of inactivity > 40 s).…”

Section: Discussionmentioning

confidence: 50%

Ethanol’s interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice

Okhuarobo

Kreifeldt

Bhattacharyya

et al. 2020

Preprint

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Large conductance potassium (BK) channels are among the most sensitive molecular targets of ethanol. Whether the action of ethanol at BK channels influences the motivation to drink alcohol remains to be determined. In the present study, we sought to investigate the behavioral relevance of this interaction by introducing in the mouse genome a point mutation (BK α K361N) known to render BK channels insensitive to ethanol while preserving their physiological function. We demonstrate that preventing ethanol′s interaction with BK channels at this site hinders the escalation of voluntary alcohol intake induced by repeated cycles of alcohol intoxication and withdrawal. In contrast, the mutation does not alter ethanol′s acute behavioral effects, nor the metabolic and activity changes induced by chronic exposure to alcohol. Our findings point at BK channel ethanol-sensing capacity as a vulnerability mechanism in the transition from moderate alcohol consumption to pathological patterns of alcohol abuse.

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“…For example, in many rodent species, oral ethanol shortens free-running circadian period (Rosenwasser et al, 2014, Seggio et al, 2009, Seggio et al, 2007) and disrupts circadian activity levels (Brager et al, 2010, Ruby et al, 2009a), while chronic intermittent ethanol (CIE) via vapor chamber does not (Logan et al, 2010). Ethanol vapor alone or mixed vapor-drinking designs markedly affect homeostatic SWS sleep but not always REM (Ehlers and Slawecki, 2000, Huitron-Resendiz et al, 2018, Veatch, 2006), while ethanol liquid diets (Kubota et al, 2002, Mukherjee et al, 2008, Mukherjee and Simasko, 2009) disrupt REM sleep in the same manner as alcohol drinking does in humans (Brower, 2001, Colrain et al, 2014, Thakkar et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Sex Differences in Photic Entrainment and Sensitivity to Ethanol‐Induced Chronodisruption in Adult Mice After Adolescent Intermittent Ethanol Exposure

Ruby

Paye

Fabi

et al. 2018

Alcoholism Clin & Exp Res

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Background: Evidence supports a role for the circadian system in alcohol use disorders, but the impact of adolescent alcohol exposure on circadian timing later in life is unknown. Acute ethanol attenuates circadian photic phase-resetting in adult, but not adolescent, rodents. However, nearly all studies have focused on males and it is unknown whether this adolescent-typical insensitivity to ethanol persists into adulthood after adolescent drinking. Methods: Circadian activity was monitored in C57BL6/J mice receiving adolescent intermittent ethanol (AIE) exposure (15% ethanol and water every other day throughout adolescence) or water alone followed by 24 days wherein ethanol was not available (washout). Mice then received a challenge dose of ethanol (1.5 g/kg, i.p.) or saline 15 min prior to a 30-min phase-delaying light pulse, then were released into constant darkness (DD). To control for possible phase-shifting by ethanol challenge alone, a separate group of mice underwent AIE exposure (or water-only) and washout, then received an ethanol or saline injection, but did not receive a light pulse prior to DD. Results: Striking sex differences in nearly all measures of circadian photic entrainment were observed during adolescence but AIE effects were subtle and few. Only ethanol-naïve adult male mice showed attenuated photic phase-shifts with ethanol challenge, while all other groups showed normal phase-resetting responses to light. AIE-exposed females showed a persistent delay in activity offset. Conclusions: Adult male AIE-exposed mice retained adolescent-like insensitivity to ethanol-induced suppression of photic phase-resetting, suggesting AIE-induced ‘lock-in’ of an adolescent behavioral phenotype. Adult AIE-exposed females showed delayed initiation of the rest phase. Our results also indicate that intermittent ethanol drinking has subtle effects on circadian activity in mice during adolescence that differ from previously reported effects on adult males. The observed sex differences in circadian activity, ethanol consumption and preference, and responses to ethanol challenge merit future mechanistic study.

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Effects of Withdrawal from Chronic Intermittent Ethanol Exposure on Sleep Characteristics of Female and Male Mice

Abstract: Our results revealed overall deficits in sleep regulation in EtOH-dependent mice of both sexes. Female mice appeared to be more affected with regard to the triggering of sleep, while male mice appeared more sensitive to disruptions in the maintenance of sleep.

Cited by 23 publications

References 68 publications

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

IL-1β expression is increased and regulates GABA transmission following chronic ethanol in mouse central amygdala

Ethanol’s interaction with BK channel α subunit residue K361 does not mediate behavioral responses to alcohol in mice

Sex Differences in Photic Entrainment and Sensitivity to Ethanol‐Induced Chronodisruption in Adult Mice After Adolescent Intermittent Ethanol Exposure

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