The effect of glutamate receptor blockade on anoxic depolarization and cortical spreading depression.
We examined the effect of blockade of N-methyl-D-aspartate (NMDA) and non-NMDA subtype glutamate receptors on anoxic depolarization (AD) and cortical spreading depression (CSD). [K+]e and the direct current (DC) potential were measured with microelectrodes in the cerebral cortex of barbiturate-anesthetized rats. NMDA blockade was achieved by injection of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate [MK-801; 3 and 10 mg/kg] or amino-7-phosphonoheptanoate (APH; 4.5 and 10 mg/kg). Non-NMDA receptor blockade was achieved by injection of 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(F)quinoxaline (NBQX; 10 and 20 mg/kg). MK-801 and APH blocked CSD, while NBQX did not. In control rats, the latency from circulatory arrest to AD was 2.1 +/- 0.1 min, while the amplitude of the DC shift was 21 +/- 1 mV, and [K+]e increased to 50 +/- 6 mM. All variables remained unchanged in animals treated with MK-801, APH, or NBQX. Finally, MK-801 (14 mg/kg) and NBQX (40 mg/kg) were given in combination to examine the effect of total glutamate receptor blockade on AD. This combination slightly accelerated the onset of AD, probably owing to circulatory failure. In conclusion, AD was unaffected by glutamate receptor blockade. In contrast, NMDA receptors play a crucial role for CSD.
Lauritzen
M
M
Department of General Physiology and Biophysics, Panum Institute, University of Copenhagen, Denmark.
Hansen
A J
AJ
D015763:2-Amino-5-phosphonovalerate / Q000031:analogs & derivatives*; D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000503:physiopathology*; D013181:Cortical Spreading Depression / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004594:Electrophysiology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017981:Receptors, Neurotransmitter / Q000037:antagonists & inhibitors / Q000502:physiology*
D000596:Amino Acids; D011810:Quinoxalines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; C031231:2-amino-7-phosphonoheptanoic acid