Studies of synaptic transmission in vivo: indirect versus direct effects of (RS)-alpha-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-propionic acid (AMPA)/kainate receptor antagonists 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo[f]quinoxaline (NBQX) and 6-cyano-7-nitro-quinoxaline-2,3-dione (CNQX) were examined by microiontophoretic administration in electrophysiological tests on spinal neurones in alpha-chloralose anaesthetized rats. The antagonists significantly reduced extracellularly recorded nociceptive and non-nociceptive responses, as expected; concurrently they reduced background 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 decreased cell excitability and only indirectly affected the test responses. Unless such indirect effects have been controlled for, the interpretation of the actions of AMPA/kainate antagonists on evoked synaptic responses is compromised and may be erroneous.