Schizophrenia (SCHZ) is a major neuropsychiatric illness, afflicting about one percent of the adult population and causing lifelong disability in many of those afflicted. Converging lines of research suggest that many SCHZ symptoms arise from excessive synaptic activity at dopamine (DA) synapses in the subcortical limbic system, particularly the nucleus accumbens (NAC). DA synaptic activity in the NAC may, in turn, be modulated by excitatory afferents from medial frontal and hippocampal cortical regions. Recent hypotheses about the etiology of SCHZ emphasize known cytoarchitectural structural defects in these cortical areas, with possible loss of cortical control of both normal DA function and efferent activity from the NAC. A major projection of the NAC is to the ventral pallidum (VP) substantia innominata. This output system primarily utilizes GABA neurons, which physiologically inhibit VP neurons. Because DA actions in the NAC are inhibitory, the net effect of increased DA synaptic activity in the NAC is to increase firing of VP neurons. Experiments in this proposal will characterize in detail the synaptic neurochemistry of excitatory amino acids (EAA) (principally glutamate) DA, and GABA in the cortical-NAC-VP pathway. Pathways will be stimulated/inhibited electrically or with drug infusion, and efflux of neurotransmitters characterized with microdialysis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29MH049875-05
Application #
2445516
Study Section
Neuropharmacology and Neurochemistry Review Committee (NPNC)
Project Start
1993-07-01
Project End
1998-06-30
Budget Start
1997-07-01
Budget End
1998-06-30
Support Year
5
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Virginia
Department
Psychiatry
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904