Phasic dopamine in reward-based learning and addiction
2007 Seed Grant
Xiaoxi Zhuang, Ph.D.
The University of Chicago
Dopamine is the common chemical mediator in the brain that mediates all addictive drugs’ rewarding properties. However, the exact role of dopamine in the two key components of reward, incentive motivation and reinforcement learning, has not been determined. This problem has significant implications in prevention and treatment of drug abuse. If dopamine mediates learning, prevention and treatment should involve extinction of learning. If dopamine mediates motivation, prevention and treatment should involve manipulation of the homeostatic motivational system. The proposed project uses a genetic approach in transgenic mice to test the hypothesis that two different activities of dopamine, the baseline tonic activity and the induced phasic activity, mediate motivation and learning respectively.
The total economic cost of drug abuse is more than half a trillion dollars annually. The most cost effective way to reduce that is prevention of drug abuse, treatment of drug abuse and prevention of relapse rather than law enforcement. That requires the understanding of the neurobiological and behavioral basis of drug abuse. One main roadblock in that aspect has been the controversy over the exact role of dopamine in addiction. The proposed project will for the first time test a key hypothesis central to such a controversy and aims to solve such a controversy. These studies will provide essential information needed to guide preventive and treatment approaches. Moreover, our studies will identify a molecular pathway and molecular targets that can be used for the development of pharmacotherapies.