Project Summary

James David Jentsch, Ph.D. (Young Investigator 2004) of University of California, Los Angeles, proposes to use micro-positron emission tomography (microPET) to quantify dopamine Dl receptor density in a putative non-human primate model for cognitive dysfunction in schizophrenia. Vervet monkeys that have been trained to perform a test of working memory will receive chronic treatment with phencyclidine (a psychotomimetic NMDA antagonist) or saline. The neurocognitive effects of chronic PCP treatment will be assessed, and dopamine Dl receptor density in the prefrontal cortex will be assessed in vivo using a tracer and microPET. Subsequently, post-mortem measures of dopamine Dl receptors and dopaminergic transmission will be made to determine the potential linkages between abnormal synaptic dopamine, dopamine Dl receptors and working memory deficits. These studies in animals will be a first step towards examining causal relationships between alterations of dopaminergic signaling determined in vivo and post mortem in humans and associated cognitive loss in schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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