Project Summary

Daniel Lodge, Ph.D. (Young Investigator 2006) of the University of Pittsburgh, will conduct an animal-model study of aberrant dopamine (DA) signaling, which is believed to play a major role in schizophrenia. Dr. Lodge has evidence that DA neuron activity states are independently regulated by distinct afferent pathways, and more recently found these pathways interact to control the population of neurons that are phasically activated. Given the central role of the hippocampus in this regulation, and evidence for hippocampal dysregulation in models of schizophrenia, Dr. Lodge proposes that a hippocampal dysfunction is the cause of DA dysregulation in schizophrenia. In the proposed project, he will study his theory in a developmental-disruption animal model of schizophrenia, in which the mitotoxin methylazoxymethanol acetate is administered to an animal during gestational day 17. The animals, which exhibit many anatomical and behavioral characteristics of schizophrenia, will then be examined as adults. Dr. Lodge will study how afferent regulation of DA neuron activity states and responsiveness to stimuli are altered in the animal model. Results should provide insights into the relationship between developmental disruption and DA neuron regulation, and information about the role of these systems in the pathophysiology of schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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