Principal Investigator:
Howard Becker, Ph.D.
Co-Principal Investigators:
Peter Kalivas, Ph.D.
Lawrence Middaugh, Ph.D.
Co-Investigator:
Patrick Randall, Ph.D.
In this basic science component, Drs. Howard Becker, Larry Middaugh, and Peter Kalivas propose to use the mouse models developed and refined during the past two ARC funding periods of alcohol self-ingestion, alcohol reward, and alcohol dependence to evaluate medications with direct or indirect effects on dopamine and glutamate activity within the "motive/reward" circuitry in brain. By measuring both dopamine and glutamate levels with microdialysis in dependent and non-dependent animals, it will be possible to determine if alcohol dependence affects these neurotransmitters differentially, and if drugs that decrease alcohol ingestion do so by altering dopamine and/or glutamate release.
Importantly, by comparing non-dependent and dependent animals, it will be possible to determine if there is a “shift” in brain chemistry associated with dependence and increased propensity for relapse. Some drugs may act in both dependent and non-dependent animals to decrease drinking, while some might act only in dependent animals.
In addition, the potential scientific contribution of this project extends beyond its findings related to pharmacotherapy, brain chemistry, and drinking. The development of reliable mouse models for alcohol related behaviors is an important contribution to the alcohol field, in general, since mice offer the unique advantage of testing specific knock-out, knock-in, and conditional knock-out animals. Mouse model systems will guide our own future experiments with genetic models and may serve as a valuable national resource. It is also expected that results from this project will guide Dr. Anton's future research in the human laboratory setting and complement Research Component #4. These basic science studies in mice have significant implications for pharmacotherapy of relapse prevention.