Selective inhibition of excitatory amino acids by divalent cations. A novel means for distinguishing N-methyl-D-aspartic acid-, kainate- and quisqualate-mediated actions in the mouse spinal cord

Biting and scratching behaviors produced by intrathecal injection of excitatory amino acid (EAA) agonists were examined to determine whether the biting and scratching behavioral effects produced by these compounds are altered selectively in vivo by coadministration with divalent cations. N-methyl-D-aspartate (NMDA)-induced behavior was inhibited by both magnesium and calcium but not by zinc. Kainic and (KA)-induced behavioral activity was also inhibited by coadministration with calcium but not by magnesium or zinc. In contrast to both NMDA and KA, calcium, magnesium and zinc failed to alter the intensity of quisqualic acid (Quis)-induced biting and scratching behaviors. Based on this selective inhibition of the three EAA subtypes by divalent cations, we examined the behavioral responses produced by Glu and Asp in combination with calcium or magnesium to identify the receptor population involved in these motor effects. Calcium antagonized the biting and scratching behavior produced by i.t. injected Glu in contrast with Asp which was inhibited significantly by magnesium. Our results support the concept that Glu and Asp produce biting and scratching behaviors by an interaction with distinct receptor populations in the spinal cord. To date, there are no selective antagonists at the KA or Quis receptors. Thus, a systematic examination of the selective inhibition of EAA activity by divalent cations in addition to currently available pharmacologic antagonists may prove to be a useful approach to the identification of NMDA, KA and Quis receptor interactions.