STUDIES OF SYNAPTIC TRANSMISSION IN-VIVO - INDIRECT VERSUS DIRECT EFFECTS OF PHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLE-PROPIONIC ACID KAINATE ANTAGONISTS ON RAT SPINAL SENSORY RESPONSES

The (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazole acid (AMPA)/kainat e receptor antagonists 3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxal ine (NBQX) and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) were exami ned by microiontophoretic administration in electrophysiological tests on spinal neurones in alpha-chloralose anaesthetized rats. The antago nists significantly reduced extracellularly recorded nociceptive and n on-nociceptive responses, as expected; concurrently they reduced backg round discharge. When the background discharge rate was held constant, the antagonists no longer significantly reduced the evoked responses. This indicates that in the absence of such control, the antagonists d ecreased cell excitability and only indirectly affected the test respo nses. Unless such indirect effects have been controlled for, the inter pretation of the actions of AMPA/kainate antagonists on evoked synapti c responses is compromised and may be erroneous.