The first two years of the proposed work will be spent investigating phencyclidine (PCP) effects in rats as a heuristic model for idiopathic psychosis in humans. In vivo intracerebral microdialysis will be used to examine the effects of PCP, and of selected PCP receptor agonists and direct N-methyl-D-aspartate (NMDA) receptor antagonists on extracellular concentrations of brain dopamine. The results will be relevant to the dopamine hypothesis of schizophrenia and may also implicate the PCP/NMDA system in the pathogenesis of schizophrenia. In the clinical part of the program, a metabolically defined """"""""psychosis circuit"""""""" will be examined by 2-deoxyglucose (2DG) autoradiography in rats given the PCP agonist ketamine or CPP, a competitive NMDA antagonist, and by use of positron emission tomography (PET) scanning in schizophrenics and normals given ketamine. This study is intended to indicate additional brain areas which should be examined in rats to PCP-induced changes in dopamine and other monamine concentrations. In clinical studies during the last three years, neuropsychological testing of normals and schizophrenics will be conducted following dosing with ketamine. Cerebrospinal fluid dopamine and homovanillic acid will be measured in schizophrenic patients given ketamine.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Physician Scientist Award (K11)
Project #
1K11MH000727-01A1
Application #
3087993
Study Section
Research Scientist Development Review Committee (MHK)
Project Start
1989-09-30
Project End
1994-08-31
Budget Start
1989-09-30
Budget End
1990-08-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Type
Schools of Medicine
DUNS #
003255213
City
Baltimore
State
MD
Country
United States
Zip Code
21201