title: Stress-induced increase in extracellular dopamine in striatum: role of glutamatergic action via N-methyl-D-aspartate receptors in substantia nigra.
abstract: There is considerable support for an influence of excitatory amino acids released from corticofugal neurons on dopaminergic activity in the basal ganglia. However, the relative importance of cortico-striatal and cortico-mesencephalic projections remains unclear, particularly with respect to the nigro-neostriatal pathway. We have therefore examined the influence of endogenous excitatory amino acids in substantia nigra on stress-induced dopaminergic activity in neostriatum. Microdialysis probes were implanted unilaterally into substantia nigra and ipsilateral neostriatum, and dopamine release in neostriatum was monitored by measuring changes in extracellular dopamine. In separate animals, neostriatal dopamine synthesis was assessed by measuring extracellular DOPA in the presence of 3-hydroxylbenzylhydrazine (NSD-1015; 100 microM), an inhibitor of aromatic amino acid decarboxylase. Thirty minutes of intermittent foot shock increased both dopamine release (+41%) and synthesis (+37%) in neostriatum. Infusion of 2-amino-5-phosphonovalerate (APV; 100 microM), an inhibitor of N-methyl-D-aspartate (NMDA) receptors, into substantia nigra greatly attenuated the stress-induced increase in neostriatal dopamine release, while having no effect on the apparent increase in stress-induced dopamine synthesis. These data suggest that excitatory amino acids such as glutamate act on NMDA receptors in substantia nigra to increase striatal dopamine release produced by exposure to stress, but that the increase in dopamine synthesis is mediated through a separate mechanism.
authors.affiliation: Departments of Neurology and Psychiatry, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: S L
authors.initials: SL
authors.lastname: Castro
authors.forename: M J
authors.initials: MJ
authors.lastname: Zigmond
mesh_terms: D000818:Animals; D004298:Dopamine / Q000096:biosynthesis* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006834:Hydrazines / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009434:Neural Pathways / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013312:Stress, Physiological / Q000378:metabolism* / Q000503:physiopathology; D013378:Substantia Nigra / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D006834:Hydrazines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; C056639:2-amino-5-phosphopentanoic acid; C004297:3-hydroxybenzylhydrazine; D014633:Valine; D004298:Dopamine