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Excitatory amino acid receptor antagonists decrease hypoxia induced increase in extracellular dopamine in striatum of
1Department of Biochemistry & Biophysics, Medical School, University of Pennsylvania, Philadelphia 19104, USA.
Neurochemistry International
|May 20, 1998
Summary
Hypoxia significantly increases extracellular dopamine in newborn piglet striatum, linked to N-methyl-D-aspartate (NMDA) receptor activation. NMDA receptor blockade with MK-801 reduces dopamine levels, suggesting a neuroprotective mechanism.
Area of Science:
- Neuroscience
- Neurochemistry
- Developmental Biology
Background:
- Hypoxia, a condition of reduced oxygen, can significantly impact brain function, particularly in developing organisms.
- Extracellular dopamine levels in the striatum are crucial for motor control and reward pathways, and their dysregulation during hypoxia is a concern.
Purpose of the Study:
- To investigate the role of excitatory amino acid receptors, specifically N-methyl-D-aspartate (NMDA) and non-NMDA receptors, in mediating the increase of extracellular striatal dopamine during hypoxia.
- To explore the potential neuroprotective mechanisms of NMDA receptor antagonists under hypoxic conditions in the neonatal brain.
Main Methods:
- Studies conducted on anesthetized, mechanically ventilated 2-3 day old piglets subjected to a hypoxic insult (inspired oxygen fraction reduced from 22% to 7%).
- In vivo microdialysis used to measure extracellular striatal dopamine levels.
- Cerebral oxygen pressure monitored optically; microdialysis probes perfused with Ringer solution, NMDA receptor antagonist MK-801, or non-NMDA receptor antagonist NBQX.
Main Results:
- Hypoxia caused a dramatic, time-dependent increase in extracellular striatal dopamine levels, reaching over 18,000% of control by the end of the hypoxic period.
- Perfusion with MK-801 significantly attenuated the hypoxia-induced rise in extracellular dopamine.
- Perfusion with NBQX showed a modest, statistically significant decrease in extracellular dopamine only at the end of the hypoxic period.
Conclusions:
- Activation of NMDA receptors, but not non-NMDA receptors, modulates the increase in extracellular striatal dopamine during hypoxia in newborn piglets.
- The NMDA receptor antagonist MK-801 may exert neuroprotective effects against hypoxic stress in the striatum by reducing extracellular dopamine levels.