Project Summary

Donald Gordon Rainnie, Ph.D. (Independent Investigator 2003) of Emory University, will determine the normal response of the basolateral nucleus (BLA), a subdivision of the amygdala, to dopamine release. This is a necessary step before determining the role of BLA in the etiology of schizophrenia. A growing body of evidence suggests that the amygdala, a structure in the temporal lobe, may play a critical role in the development and expression of many of the emotional problems associated with schizophrenia. Hence, damage to the amygdala in infancy results in the development of behavioral deficits that are common to schizophrenia, and, like schizophrenia, only become manifest after puberty. In addition, functional disconnection of the pathway between the amygdala and the prefrontal cortex results in specific deficits in goal directed behavior. Moreover, dopamine levels are elevated in the amygdala of schizophrenic patients, and functional imaging studies have shown a reduced metabolic activity in the amygdala of these patients that correlates with symptom expression and is associated with an allelic variant of the dopamine D1 receptor, and which can be reversed following treatment with the atypical antipsychotic agent, clozapine. Together, these data strongly support the hypothesis that a dysfunction of dopaminergic transmission within the amygdala may contribute to the development and expression of schizoaffective behavior. The basolateral nucleus (BLA) is implicated as it sends and receives direct input to and from the prefrontal cortex. If a dopamine-mediated breakdown in communication between the amygdala and the prefrontal cortex is truly a contributory factor to the etiology of schizophrenia, then we would expect this breakdown to be manifest in the function of the BLA. There is little is known about the physiological consequences of dopamine receptor activation in individual neurons of the BLA, arid how this impacts upon the normal function of the nucleus. Dr. Rainnie will address this issue, to determine the effects of acute and chronic clozapine treatment on the response of BLA neurons to dopamine. He hopes to establish a database of normative data for dopamine function in the BLA to better understand how pathophysiological changes in BLA function could contribute to the development of schizophrenia.

Program Area: SCHIZOPHRENIA/PSYCHOTIC DISORDERS\Schizophrenia

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