Learning and Addiction

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.

Other Grants

Lindsay M. De Biase, Ph.D., University of California Los Angeles
The role of microglial lysosomes in selective neuronal vulnerability
Synapses, the sites of signaling between neurons in the brain, play essential roles in learning, memory, and the health of neurons themselves. An enduring mystery is why some neurons are…
How the nervous system constructs internal models of the external world
As animals navigate their environments, they construct internal models of the external sensory world and use these models to guide their behavior. This ability to incorporate ongoing sensory stimuli into…
Xiaojing Gao, Ph.D., Stanford University
When Neural Circuits Meet Molecular Circuits: Quantitative Genetic Manipulation with Single-cell Consistency
Cells are the building blocks of our bodies. We get sick when the cells “misbehave”. The way modern gene therapies work is to introduce genes, fragments of DNA molecules that…
Rafiq Huda, Ph.D., Rutgers University
Conducting the orchestra of movement—functional role of striatal astrocytes in health and disease
Movement requires coordinated activity across a large brain-wide network. The striatum is a particularly important part of this circuit; it integrates motor-related information from many distinct brain regions to regulate…