Specific Aims

The primary goals of our Animal Models Core are to ensure that standardized behavioral and biochemical operating procedures are used across laboratories, to provide animals dependent on alcohol using the chronic intermittent ethanol (CIE) vapor exposure model and blood alcohol level (BAL) determinations to investigators who do not have the expertise or capability to otherwise obtain these animals or perform these assays, and to extend and refine mouse CIE models using newly developed techniques. Personalized consultation with investigators on issues related to experimental design, sample collection, and sample handling also will be provided. We are proposing to run the Core at TSRI only (instead of having two sites as in the previous funding period) with partially new leadership (Project Lead: Dr. Roberts, Co-Lead: Dr. Zorrilla) in order to achieve our goals of centralizing and standardizing our services and support the increased use of mice by the ARC.

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Specific Aim 1

To provide animals that are dependent or have a history of dependence to TSRI-ARC and Center-at-Large investigators. The main goal of this Specific Aim is to provide animals that are engaged in excessive drinking using the CIE model or animals only exposed to CIE and not the drinking procedures to TSRI-ARC investigators and secondarily to Center-at-Large investigators. Another goal is to supervise all changes in equipment and procedures and any refinement of the current animal models to ensure that standardized procedures are used across all laboratories. In this renewal, we are adding additional mouse vapor chamber capacity to meet the needs of three research components, for developmental Core work, and as an added resource for Center-at-Large investigators.

Specific Aim 2: To provide blood alcohol level analysis to TSRI-ARC and Center-at-Large investigators. The goal of this aim is to provide BAL services to investigators who do not have the expertise or equipment to otherwise obtain these measures and provide these for Core-run experiments in Specific Aim 1 (i.e., maintaining target BALs in CIE experiments) and Specific Aim 3 (developmental mouse CIE experiments). We have optimized our gas chromatograph (GC) system and the means to request this service and provide BAL data back to the requestor in a timely and efficient manner.

 

Specific Aim 3

To extend and refine the mouse chronic intermittent ethanol model using newly developed techniques. The goals of this aim are to extend and strengthen the phenotypic characterization of withdrawal and protracted abstinence in the mouse CIE model and examine a strategy for removing the need for pyrazole + alcohol injections prior to vapor exposure. We will implement in-cage video recording to monitor behavioral patterns and then assemble matrices of innate behaviors for subsequent statistical analyses in order to compare control and CIE mice. We will include conditions of novelty in these experiments, as responses to change appear to be altered by CIE. We also will develop a labyrinth-style maze to investigate exploratory patterns and learning strategies (e.g., to find alcohol) in CIE vs. control mice. Finally, we will analyze BALs across CIE cycles in mice and throughout withdrawal and explore ways of achieving this same exposure pattern without the need for pyrazole/alcohol pretreatments.

 

Significance and value to the ARC

The Animal Models Core will provide critical services to all ARC research components by producing CIE rats and mice and performing BAL analyses needed for the proposed experiments. The centralization of these services prevents unnecessary duplication of resources and effort, thereby providing substantial time- and cost-savings for Research Components utilizing the Core services. Centralized services also provide standardized quality control and increased consistency across projects. The Core will continue to have a strong scientific component, in this case applying novel techniques in mouse behavioral assessment to the CIE model. The Animal Models Core will promote integrative, efficient, and high-quality research that is the foundation of the ARC research goals and mission.