Effects of N-methyl-D-aspartate-receptor blockade on high-potassium-induced neuronal death and glutamate release.
Microdialysis probe delivery of an isotonic high-K+ solution to the rat amygdala for 60-70 min produces neuronal necrosis, edematous neuropil and increases in extracellular glutamate and aspartate. In this study we determined the effects of the competitive N-methyl-D-aspartate (NMDA)-receptor antagonist CGP 40116. Bilateral microdialysis probes were inserted through previously placed guide cannulae in the basolateral amygdaloid nuclei of adult Wistar rats. Following a 2 h baseline perfusion in freely-moving rats, the solution was switched bilaterally for 60-70 min to an isotonic 100 mM K+ solution; 12% of the 100 mM K+ is extracted by tissue. One side contained either 36 or 360 microM CGP 40116 during baseline and high-K+ perfusion, of which 42 and 48% were extracted respectively. Although neither concentration reduced tissue edema, 360 microM CGP 40116 was neuroprotective and prevented the high-K+-induced elevations of glutamate.
Fujikawa
D G
DG
Experimental Neurology Laboratory, VA Medical Center (151B4), Sepulveda, CA 91343, USA. dfujikaw@ucla.edu
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives* / Q000494:pharmacology; D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D016923:Cell Death / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000378:metabolism*; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D018691:Excitatory Amino Acid Antagonists; C064539:2-amino-4-methyl-5-phosphono-3-pentenoic acid; D018698:Glutamic Acid; D015763:2-Amino-5-phosphonovalerate; D011188:Potassium