Animal Models Core

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PROJECT SUMMARY/ABSTRACT– ANIMAL MODELS CORE A main objective of the Animal Models Core is to provide a broad range of behavioral assays of stimulant and opiate action in mice and rats to support the PPG’s overall goal to establish the molecular and cellular basis of addiction. Such assays include several routine behavioral tests as well as more sophisticated self- administration and relapse procedures. It is crucial to employ a broad behavioral battery since it is difficult to infer something about a complex behavioral syndrome like addiction from a single model or even a limited number of models. The Core then utilizes these behavioral resources in two main ways. First, the Core provides microdissections of brain reward regions from rodents that self-administer cocaine or heroin for molecular-cellular characterization in each Project and the Gene and Chromatin Analysis Core. Second, the Core works with each of the four Projects to generate causal evidence that directly links specific molecular and cellular adaptations to particular behavioral abnormalities that define a state of addiction. The Core accomplishes this goal by providing a range of genetic mutant mice as well as a large number of vectors for viral-mediated gene transfer, all of which are extensively validated by the Core. The mutant mice and viral vectors, often generated initially to meet the specific needs of an individual Project, are then provided to other Projects to broaden their application and thereby promote PPG integration. PPG investigators have led the field in generating mutant mice and viral vectors, which make it possible to selectively manipulate a given gene of interest within a particular cell type and brain region of adult animals, thus avoiding confounds with more traditional approaches. Finally, the Core provides advanced neurophysiology, optogenetic, and fiber photometry tools to Project investigators to directly relate altered molecular-cellular function to addiction- related behavioral abnormalities. By consolidating this behavioral, mouse mutant, viral vector, and other work within a centralized Core, we ensure rigorous control over the data and facilitate comparisons and contrasts of experimental results across the individual Projects. This consolidation also makes financial sense, since we concentrate and maximize efficient use of the required expertise.