The triggering of spreading depression in the chicken retina: a pharmacological study

Spreading depression (S.D.) can be reproducibly evoked in the retinas of 3- to 6-day-old chickens by K+ ions, N-methyl-D-aspartate (NMDA), kainate (KA), and quisqualate (QA). Specific NMDA antagonists inhibit S.D. evoked by all the above agents. The very selective non-NMDA receptor antagonist 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)quinoxaline (NBQX) blocks QA- and KA-evoked S.D. but not NMDA- or K(+)-evoked S.D. These findings indicate that NMDA receptor activation is the vital event in the triggering of S.D. in this tissue, and that QA and KA trigger S.D. indirectly via excitation of NMDA receptors. Tetrodotoxin, cadmium chloride, conotoxin, baclofen and adenosine agonists are all ineffective in blocking K(+)-, NMDA-, QA- or KA-evoked S.D. L-trans-Pyrrolidine-2,4-dicarboxylic acid, a glutamate uptake blocker, does inhibit QA-evoked S.D. It is therefore argued that a presynaptic release of vesicular, glutamate 'neurotransmitter stores' is not the mechanism of action of QA and KA. A mechanism involving a reversal of the glutamate uptake carrier is suggested.