Project Summary

Patrick B. Allen, Ph.D. (Young Investigator 2005) of Connecticut Mental Health Center and Yale University, plans to use knockout mice to study how the neurotransmitter dopamine acts on glutamate neurotransmission system in the brain. Current schizophrenia treatments employ drugs that block dopamine’s actions, but how these drugs achieve their beneficial effects is not known. Recent work, though, shows dopamine has a profound effect on the glutamate system. Glutamate receptors exist on the surface of neurons in the central nervous system, and the cell-surface occupancy of these receptors, and hence their activity, is regulated dynamically. Dopamine exerts its action by activating specific biochemical signaling processes, such as the phosphatase enzyme, within neurons. In this study, Dr. Allen proposes to examine the regulation of phosphatase and its influence over glutamate receptor activity and cell surface occupancy using genetically modified mouse strains where the relevant genes have been deleted. These animals and their normal counterparts will undergo drug treatments that influence dopamine and glutamate neurotransmission. These studies could identify biochemical processes involved in antipsychotic drug action, and may lead to the design of drugs with greater specificity and fewer side effects.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia\Molecular

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