Effects of ionotropic glutamate receptor blockade and 5-HT1A receptor activation on spreading depression in rat neocortical slices.
The effect of the AMPA antagonist NBQX (10 microM), NMDA antagonist ketamine (100 microM) and 5-HT1A agonist 8-OH-DPAT (1, 10 and 100 microM) on the properties of a KCl-induced spreading depression (SD) was studied in parietal cortical slices of adult rats. Whereas NBQX did not significantly affect the SD, ketamine significantly (p < 0.01) reduced the amplitude of the first SD peak (12.8 +/- 4.6 mV) and blocked the second SD peak when compared with the controls (19.8 +/- 5.2 mV and 25 +/- 5 mV, respectively). Ketamine also decreased the SD duration at half maximal amplitude from 34.9 +/- 12.4 s to 22.2 +/- 12 s (p < 0.05). 8-OH-DPAT attenuated the duration of the SD from 42 +/- 15.6 s to 21.2 +/- 10.6 s (p < 0.05, 100 microM). These data indicate that not only NMDA receptor blockade, but also activation of the 5-HT1A receptor attenuates the SD and may be beneficial in the reduction of ischemic injury following focal cerebral ischemia.
Krüger
H
H
Institute of Physiology, Department of Neurophysiology, Charité, Berlin, Germany.
Heinemann
U
U
Luhmann
H J
HJ
D000818:Animals; D013181:Cortical Spreading Depression / Q000187:drug effects*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D066298:In Vitro Techniques; D007649:Ketamine / Q000494:pharmacology; D019579:Neocortex / Q000187:drug effects*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D018691:Excitatory Amino Acid Antagonists; D011810:Quinoxalines; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D017366:Serotonin Receptor Agonists; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D007649:Ketamine