Heavy alcohol drinking and binge drinking are patterns of alcohol consumption considered abusive and which are associated with increased risk of injuries, physical maladies, mental illness, and increased risk of dependence upon alcohol. Once dependent, alcohol abuse becomes chronic;with strong craving, continued use despite physical, psychological and social problems, and loss of control over intake. Excessive drinking is a hallmark of both abuse and dependence. INIA-West has focused on excessive alcohol drinking as a target for animal model development, cellular and molecular investigation, and, ultimately, on medications target identification. While there are currently three FDA approved medications for alcohol dependence available, disulfiram, naltrexone, and acamprosate, there is still a push by NIAAA to identify more efficacious pharmacotherapies to combat the deleterious effects of heavy alcohol consumption and alleviate those effects that lead to continued intake and relapse. The overarching theme of the Mouse Target Assessment Core is to use INIA models of excessive alcohol drinking and the behavioral effects of alcohol to explore targets that have been identified over the past funding periods. The specific goals of the Mouse Target Assessment Core (MTAC) are to: 1) Continue to optimize and extend INIA models of excessive drinking and provide test services and tissues to consortium investigators;2) Identify and test new target compounds based on INIA-West-generated data;2) Improve in vivo testing of potential pharmacotherapeutic targets;3) Work closely with the Rat Target Assessment Core (Kosten) and the Rat Animal Models and Gene Testing Core (Bell) to standardize our target identification in a cross-species manner;4) Work with INIA investigators as targets are identified and with the Steering Committee and Scientific Advisory Board to prioritize them for testing and determine which to pursue further;and 5) Use RNA interference (RNAi) technology and genetically engineered mice to examine target systems for which usable compounds are, as yet, unavailable as well as to confirm and extend positive results.

Public Health Relevance

Excessive alcohol drinking is a major public health problem that has been the focus of research by the Integrative Neurosciences Initiative on Alcoholism (INIA-West) consortium. We now have robust mouse models and a list of potential therapeutic targets based on this work. The goal of the Mouse Target Assessment Core is to explore the effects of manipulating INIA targets in these excessive drinking models.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project--Cooperative Agreements (U01)
Project #
5U01AA020893-04
Application #
8718953
Study Section
Special Emphasis Panel (ZAA1)
Program Officer
Egli, Mark
Project Start
2011-09-05
Project End
2016-08-31
Budget Start
2014-09-01
Budget End
2015-08-31
Support Year
4
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Sanna, P P; Kawamura, T; Chen, J et al. (2016) 11β-hydroxysteroid dehydrogenase inhibition as a new potential therapeutic target for alcohol abuse. Transl Psychiatry 6:e760
Hernandez, Ruben V; Puro, Alana C; Manos, Jessica C et al. (2016) Transgenic mice with increased astrocyte expression of IL-6 show altered effects of acute ethanol on synaptic function. Neuropharmacology 103:27-43
Schweitzer, Paul; Cates-Gatto, Chelsea; Varodayan, Florence P et al. (2016) Dependence-induced ethanol drinking and GABA neurotransmission are altered in Alk deficient mice. Neuropharmacology 107:1-8
Herman, Melissa A; Sidhu, Harpreet; Stouffer, David G et al. (2015) GIRK3 gates activation of the mesolimbic dopaminergic pathway by ethanol. Proc Natl Acad Sci U S A 112:7091-6
Kreifeldt, Max; Cates-Gatto, Chelsea; Roberts, Amanda J et al. (2015) BK Channel β1 Subunit Contributes to Behavioral Adaptations Elicited by Chronic Intermittent Ethanol Exposure. Alcohol Clin Exp Res 39:2394-402
Bajo, Michal; Varodayan, Florence P; Madamba, Samuel G et al. (2015) IL-1 interacts with ethanol effects on GABAergic transmission in the mouse central amygdala. Front Pharmacol 6:49
Hauser, Sheketha R; Hedlund, Peter B; Roberts, Amanda J et al. (2014) The 5-HT7 receptor as a potential target for treating drug and alcohol abuse. Front Neurosci 8:448
Gruol, Donna L; Vo, Khanh; Bray, Jennifer G et al. (2014) CCL2-ethanol interactions and hippocampal synaptic protein expression in a transgenic mouse model. Front Integr Neurosci 8:29
Vendruscolo, Leandro F; Roberts, Amanda J (2014) Operant alcohol self-administration in dependent rats: focus on the vapor model. Alcohol 48:277-86
Bray, Jennifer G; Reyes, Kenneth C; Roberts, Amanda J et al. (2013) Synaptic plasticity in the hippocampus shows resistance to acute ethanol exposure in transgenic mice with astrocyte-targeted enhanced CCL2 expression. Neuropharmacology 67:115-25

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