Temperature regulation in mice during withdrawal from ethanol dependence

Crawshaw, Larry I.; O'Connor, Candace S.; Crabbe, John Jr; Hayteas, David L.

doi:10.1152/ajpregu.1994.267.4.r929

Cited by 7 publications

(13 citation statements)

References 8 publications

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“…Results from Experiments 3 and 4 revealed that effects of chronic EtOH withdrawal on nest building were more pronounced during early stages of withdrawal (i.e., the first 24 h) when EtOH withdrawal-induced reductions in thermal set point have been observed. HS/Ibg mice were generally more motivated to seek cooler environments when tested in thermal gradients 1–26 h after chronic EtOH vapor inhalation, and this change in preference occurred in the absence of reduced core body temperature [13]. EtOH-withdrawing mice also displayed greater variability in preferred temperatures than either mice that breathed air and had been given daily injections of pyrazole in saline or injections of saline alone during the initial 10–11 hours after exiting the vapor chambers.…”

Section: Discussionmentioning

confidence: 99%

“…These states are disrupted in mice over various time periods during withdrawal from chronic EtOH. During the initial 24 hours of withdrawal from three days of chronic EtOH vapor inhalation, dysregulated body temperature [13] and motor abnormalities (e.g., increased tremor) [14] were observed in mice from a genetically heterogeneous stock and in mice selectively bred for severe EtOH withdrawal HICs, respectively. Longer-lasting motor impairments on the balance beam and accelerating rotarod were dose-dependently induced by chronic EtOH vapor inhalation and observed up to 3 days after withdrawal in mice from a genetically segregating background [15].…”

Section: Introductionmentioning

confidence: 99%

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Nest building is a novel method for indexing severity of alcohol withdrawal in mice

Greenberg

Huang

Spence

et al. 2016

Behavioural Brain Research

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Withdrawal after chronic ethanol (EtOH) affects body temperature, goal-directed behavior and motor function in mice and increases general central nervous system excitability. Nest-building tests have been used to assay these states but to this point have not been employed as measures of EtOH withdrawal severity. We first refined nest-scoring methods using a genetically heterogeneous stock of mice (HS/Npt). Mice were then made physically dependent following three days of chronic EtOH vapor inhalation to produce average blood EtOH concentrations (BECs) of 1.89 mg/mL. EtOH withdrawal affected the progression of nest building over time when mice were tested 2–4 days after removal from three days of chronic exposure to EtOH. In a separate group of mice, chronic EtOH vapor inhalation (BECs 1.84 mg/mL) suppressed nest building over days 1–2 but not days 2–3 of withdrawal. In a following experiment, EtOH withdrawal dose-dependently slowed recovery of nest building for up to 32 h. Finally, we determined that long-lasting nest-building deficits extend to mice undergoing withdrawal from a high dose (4g/kg) of acute EtOH. Sex differences for nest building were absent following EtOH exposure. In mice naïve to EtOH treatments, male mice had lower pre-test body temperatures and increased nest scores across a two-day testing period compared to females. These results suggest that nest building can be used to assess chronic and acute EtOH withdrawal severity in mice.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Nest building is a novel method for indexing severity of alcohol withdrawal in mice

Greenberg

Huang

Spence

et al. 2016

Behavioural Brain Research

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“…Briefly, using WD Battery 1, we sought to replicate in HS/Npt mice multiple withdrawal-sensitive behaviors shown previously at approximately these hours of WD to reflect treatment effects (Kosobud & Crabbe, 1986; Crabbe et al, 2012; Philibin et al, 2008). We also included a test of anxiety-like behavior (Gorin et al, 2005) and assessed body temperatures (Crawshaw et al, 1994). Based on the results of WD Battery 1 (see Results, Anxiety-Like Behavior), we designed WD Battery 2 to test anxiety-like behavior without previously testing other withdrawal signs, followed by body temperature to verify the previous findings, and added a sucrose preference test to assess possible anhedonia (Muscat and Willner, 1992).…”

Section: Methodsmentioning

confidence: 99%

An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice

Metten

Schlumbohm

Huang

et al. 2018

Alcohol

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Despite acceptance that risk for alcohol-use disorder (AUD) has a large genetic component, the identification of genes underlying various components of risk for AUD has been hampered in humans, in part by the heterogeneity of expression of the phenotype. One aspect of AUD is physical dependence. Alcohol withdrawal is a serious consequence of alcohol dependence with multiple symptoms, many of which are seen in multiple species, and can be experienced over a wide-ranging time course. In the present three studies, we developed a battery of withdrawal tests in mice, examining behavioral symptoms from multiple domains that could be measured over time. To permit eventual use of the battery in different strains of mice, we used male and female mice of a genetically heterogeneous stock developed from intercrossing eight inbred strains. Withdrawal symptoms were assessed using commonly used tests after administration of ethanol in vapor for 72 continuous hours. We found significant effects of ethanol withdrawal versus air-breathing controls on nearly all symptoms, spanning 4 days following ethanol vapor inhalation. Withdrawal produced hypothermia, greater neurohyperexcitability (seizures and tremor), anxiety-like behaviors using an apparatus (such as reduced transitions between light and dark compartments), anhedonia (reduced sucrose preference), Straub tail, backward walking, and reductions in activity; however, there were no changes in thermal pain sensitivity, hyper-reactivity to handling, or anxiety-like emergence behaviors in other apparatus. Using these data, we constructed a refined battery of withdrawal tests. Individual differences in severity of withdrawal among different tests were weakly correlated at best. This battery should be useful for identifying genetic influences on particular withdrawal behaviors, which should reflect the influences of different constellations of genes.

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“…These include tachycardia (increased heart rate), increased blood pressure, diaphoresis (heavy sweating), body temperature dysregulation, and gastrointestinal disturbances (nausea, vomiting). Animal models demonstrate many of these classic sympathomimetic withdrawal symptoms, including altered cardiovascular function, central and behavioral thermal dysregulation, diarrhea, and reduced food and water intake (Crawshaw et al 1994; Friedman 1980; Rasmussen et al 2006). However, given the complex and dynamic nature of variables that influence autonomic function, the reliability and practical utility of these measures is questionable (Bar et al 2006).…”

Section: Modeling Human Withdrawal Phenotypes In Animalsmentioning

confidence: 99%

REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?

et al. 2010

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The role of withdrawal-related phenomena in development and maintenance of alcohol addiction remains under debate. A “self-medication” framework postulates that emotional changes are induced by a history of alcohol use, persist into abstinence, and are a major factor in maintaining alcoholism. This view initially focused on negative emotional states during early withdrawal: these are pronounced, occur in the vast majority of alcohol dependent patients, and are characterized by depressed mood and elevated anxiety. This concept lost popularity with the realization that, in most patients, these symptoms abate over 3 – 6 weeks of abstinence, while relapse risk persists long beyond this period. More recently, animal data have established that a prolonged history of alcohol dependence induces more subtle neuroadaptations. These confer altered emotional processing that persists long into protracted abstinence. The resulting behavioral phenotype is characterized by excessive voluntary alcohol intake and increased behavioral sensitivity to stress. Emerging human data support the clinical relevance of negative emotionality for protracted abstinence and relapse. These developments prompt a series of research questions: 1) Are processes observed during acute withdrawal, while transient in nature, mechanistically related to those that remain during protracted abstinence? 2) Is susceptibility to negative emotionality in acute withdrawal in part due to heritable factors, similar to what animal models have indicated for susceptibility to physical aspects of withdrawal? 3) To what extent is susceptibility to negative affect that persists into protracted abstinence heritable?

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Temperature regulation in mice during withdrawal from ethanol dependence

Cited by 7 publications

References 8 publications

Nest building is a novel method for indexing severity of alcohol withdrawal in mice

Nest building is a novel method for indexing severity of alcohol withdrawal in mice

An alcohol withdrawal test battery measuring multiple behavioral symptoms in mice

REVIEW: Acute withdrawal, protracted abstinence and negative affect in alcoholism: are they linked?

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