title: Nest building is a novel method for indexing severity of alcohol withdrawal in mice.
abstract: 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 (4 g/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.
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; Portland Alcohol Research Center, Portland, OR, USA; VA Portland Health Care System, Portland, OR, USA. Electronic address: greenbeg@ohsu.edu.
authors.forename: G D
authors.initials: GD
authors.lastname: Greenberg
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; Portland Alcohol Research Center, Portland, OR, USA; VA Portland Health Care System, Portland, OR, USA.
authors.forename: L C
authors.initials: LC
authors.lastname: Huang
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; Portland Alcohol Research Center, Portland, OR, USA; VA Portland Health Care System, Portland, OR, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Spence
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; Portland Alcohol Research Center, Portland, OR, USA; VA Portland Health Care System, Portland, OR, USA.
authors.forename: J P
authors.initials: JP
authors.lastname: Schlumbohm
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; Portland Alcohol Research Center, Portland, OR, USA; VA Portland Health Care System, Portland, OR, USA.
authors.forename: P
authors.initials: P
authors.lastname: Metten
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; Portland Alcohol Research Center, Portland, OR, USA; VA Portland Health Care System, Portland, OR, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Ozburn
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, USA; Portland Alcohol Research Center, Portland, OR, USA; VA Portland Health Care System, Portland, OR, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Crabbe
mesh_terms: D020751:Alcohol-Induced Disorders / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002492:Central Nervous System Depressants / Q000097:blood / Q000633:toxicity*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004333:Drug Administration Routes; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009425:Nesting Behavior / Q000187:drug effects / Q000502:physiology*; D013375:Substance Withdrawal Syndrome / Q000235:genetics / Q000503:physiopathology*; D013997:Time Factors
chemical_list: D002492:Central Nervous System Depressants; D000431:Ethanol
keywords: Acute; Chronic; Ethanol; Mice; Nest; Withdrawal