Mf. Kuo et al., EXCITATORY AMINO-ACID RECEPTOR ANTAGONISTS DECREASE HYPOXIA-INDUCED INCREASE IN EXTRACELLULAR DOPAMINE IN STRIATUM OF NEWBORN PIGLETS, Neurochemistry international, 32(3), 1998, pp. 281-289
The present study tested the hypothesis that the increase in extracell
ular striatal dopamine during hypoxia is least partly associated with
activation of N-methyl-D-aspartate (NMDA) and/or non-NMDA excitatory a
mino acid receptors. Studies were performed in anesthetized and mechan
ically ventilated 2-3 days old piglets. Hypoxic insult was induced by
decreasing the oxygen fraction in inspired gas (FiO(2)) from 22 to 7%
for 1 h, followed by 1 h reoxygenation at 22%. Cortical oxygen pressur
e was measured optically by oxygen dependent quenching of phosphoresce
nce, and extracellular striatal dopamine was measured using in vivo mi
crodialysis. The microdialysis probes were perfused with Ringer soluti
on +/-50 mu M 0,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine malea
te (MK-801) or 50 mu M -dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxal
ine (NBQX). One hour of hypoxia decreased the cortical oxygen pressure
from 46+/-3 Torr to 10+/-1.8 Torr. In striatum perfused with Ringer,
statistically significant increase in extracellular dopamine, to 1050/-310% of control, was observed after 20 min of hypoxia. By 40 min of
hypoxia the extracellular level of dopamine increased to 4730+/-900% o
f control; by the end of the hypoxic period the values increased to 18
451/1670% of control. The presence of MK-801 in the perfusate signific
antly decreased the levels of extracellular dopamine during hypoxia. A
t 20, 40 and 60 min of hypoxia extracellular level of dopamine increas
ed to 278+/-94% of control, 1530+/-339% of control and 14709+/-1095 of
control, respectively. The presence of NBQX caused a statistically si
gnificant decrease, by about 30%, in the extracellular dopamine compar
ed to control, only at the end of the hypoxic period. It can be conclu
ded that in striatum of newborn piglets, the excitatory NMDA receptors
but not the non-NMDA receptors may be modulating the changes in extra
cellular levels of dopamine. The NMDA receptor antagonist. MK-801, may
exert part of its reported neuroprotective effect to hypoxic stress i
n striatum by decreasing the levels of extracellular dopamine. (C) 199
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