We are selectively breeding mice that drink sufficient EtOH to achieve high (>100 mg%) blood ethanol concentrations (BECs) during a 4 hr exposure to 20% EtOH. The HDID-1 line will be in its 20th selected generation (S20) at the time of the renewal. A second replicate (HDID-2) was started in Year 6 and will be in generation S13. The principal goal of this renewal is to continue to select these two lines. As animals are selected, we will breed additional naive mice each generation and ship them to other INIA-West investigators for their specific aims, as well as to other interested investigators. To assess pleiotropic gene effects, we will characterize the HDID lines and their HS/Npt control line for several responses to ethanol. Co-I Tamara Phillips is examining the circuitry underlying DID, using intracranial injection of test compounds to inactivate specific brain areas temporarily. Use of transmitter-specific drugs will also be considered in regions where inactivation is effective for manipulation of afferent or efferent pathways based on INIA-West targeted circuits. As relevant brain areas are identified, we will explore how intracranial injections modulate drinking microstructure. With a supplement, we obtained equipment to assess feeding and drinking microstructure simultaneously and will analyze this in the lines. We will test the hypothesis that drinking following chronic intermittent exposure to ethanol vapor is enhanced in HDID mice. The microstructure of drinking will also be explored during this post-CIE drinking.
This project addresses goals related to etiology and prediction of risk of alcohol abuse, alcoholism, and specific alcohol-related health problems. The genetic risk and protective markers that we are studying will be of utility in the future for prevention and treatment of alcoholism.
|Crabbe, John C; Schlumbohm, Jason P; Hack, Wyatt et al. (2016) Fear conditioning in mouse lines genetically selected for binge-like ethanol drinking. Alcohol 52:25-32|
|Cozzoli, Debra K; Courson, Justin; Rostock, Charlotte et al. (2016) Protein Kinase C Epsilon Activity in the Nucleus Accumbens and Central Nucleus of the Amygdala Mediates Binge Alcohol Consumption. Biol Psychiatry 79:443-51|
|Greenberg, G D; Crabbe, J C (2016) Gene Targeting Studies of Hyperexcitability and Affective States of Alcohol Withdrawal in Rodents. Int Rev Neurobiol 126:357-90|
|Greenberg, G D; Huang, L C; Spence, S E et al. (2016) Nest building is a novel method for indexing severity of alcohol withdrawal in mice. Behav Brain Res 302:182-90|
|Crabbe, John C (2016) Progress With Nonhuman Animal Models of Addiction. J Stud Alcohol Drugs 77:696-9|
|Greenberg, Gian D; Phillips, Tamara J; Crabbe, John C (2016) Effects of acute alcohol withdrawal on nest building in mice selectively bred for alcohol withdrawal severity. Physiol Behav 165:257-66|
|Phillips, T J; Mootz, J R K; Reed, C (2016) Identification of Treatment Targets in a Genetic Mouse Model of Voluntary Methamphetamine Drinking. Int Rev Neurobiol 126:39-85|
|Barkley-Levenson, Amanda M; Ryabinin, Andrey E; Crabbe, John C (2016) Neuropeptide Y response to alcohol is altered in nucleus accumbens of mice selectively bred for drinking to intoxication. Behav Brain Res 302:160-70|
|Barkley-Levenson, Amanda M; Cunningham, Christopher L; Smitasin, Phoebe J et al. (2015) Rewarding and aversive effects of ethanol in High Drinking in the Dark selectively bred mice. Addict Biol 20:80-90|
|Phillips, T J; Reed, C; Pastor, R (2015) Preclinical evidence implicating corticotropin-releasing factor signaling in ethanol consumption and neuroadaptation. Genes Brain Behav 14:98-135|
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