title: Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking.
abstract: The comorbidity of substance- and alcohol-use disorders (AUD) with other psychiatric conditions, especially those related to stress such as post-traumatic stress disorder (PTSD), is well-established. Binge-like intoxication is thought to be a crucial stage in the development of the chronic relapsing nature of the addictions, and self-medication through binge-like drinking is commonly seen in PTSD patients. We have selectively bred two separate High Drinking in the Dark (HDID-1 and HDID-2) mouse lines to reach high blood ethanol concentrations (BECs) after a 4-h period of access to 20% ethanol starting shortly after the onset of circadian dark. As an initial step toward the eventual goal of employing binge-prone HDID mice to study PTSD-like behavior including alcohol binge drinking, we sought first to determine their ability to acquire conditioned fear. We asked whether these mice acquired, generalized, or extinguished conditioned freezing to a greater or lesser extent than unselected control HS/Npt mice. In two experiments, we trained groups of 16 adult male mice in a standard conditioned fear protocol. Mice were tested for context-elicited freezing, and then, in a novel context, for cue-induced freezing. After extinction tests, renewal of conditioned fear was tested in the original context. Mice of all three genotypes showed typical fear responding. Context paired with shock elicited freezing behavior in a control experiment, but cue unpaired with shock did not. These studies indicate that fear learning per se does not appear to be influenced by genes causing predisposition to binge drinking, suggesting distinct neural mechanisms. However, HDID mice are shown to be a suitable model for studying the role of conditioned fear specifically in binge-like drinking.
authors.affiliation: Portland Alcohol Research Center, VA Portland Health Care System, Portland, OR 97239, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA. Electronic address: crabbe@ohsu.edu.
authors.forename: John C
authors.initials: JC
authors.lastname: Crabbe
authors.affiliation: Portland Alcohol Research Center, VA Portland Health Care System, Portland, OR 97239, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Jason P
authors.initials: JP
authors.lastname: Schlumbohm
authors.affiliation: Portland Alcohol Research Center, VA Portland Health Care System, Portland, OR 97239, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Wyatt
authors.initials: W
authors.lastname: Hack
authors.affiliation: Portland Alcohol Research Center, VA Portland Health Care System, Portland, OR 97239, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Barkley-Levenson
authors.affiliation: Portland Alcohol Research Center, VA Portland Health Care System, Portland, OR 97239, USA; Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: Pamela
authors.initials: P
authors.lastname: Metten
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
authors.forename: K Matthew
authors.initials: KM
authors.lastname: Lattal
mesh_terms: D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology*; D000818:Animals; D063425:Binge Drinking / Q000235:genetics* / Q000523:psychology*; D003213:Conditioning, Psychological / Q000502:physiology; D005239:Fear / Q000502:physiology / Q000523:psychology*; D008297:Male; D051379:Mice; D011897:Random Allocation; D013045:Species Specificity
keywords: Conditioned fear; Drinking in the dark; Ethanol binge drinking; Genetics; Mouse; Selective breeding