THE EFFECTS OF CYCLIC DICARBOXYLIC-ACIDS ON SPONTANEOUS AND AMINO-ACID EVOKED ACTIVITY OF RAT CORTICAL-NEURONS

A series of cyclic dicarboxylic acids were applied by microiontophoresis of neurons in the cerebral cortex of rats anesthetized with urethane. Effects on spontaneous firing rates and any ability to antagonize responses to excitatory amino acids were examined. At relatively low ejecting currents (10-25 nA), cis-2,3-piperidine dicarboxylic acid (cis-2,3-PDA) had no effect on spontaneous firing but selectively antagonized the excitation evoked by N-methyl-D-aspartate (NMDA) without affecting responses to quisqualate or kainate. At higher ejecting currents (60-100 nA) responses to all 3 agonists were reduced. Other cis-piperidine dicarboxylic acids and piperazine-2,3-dicarboxylic acid had only weak and variable effects on cell firing and responses to NMDA, quisqualate, kainate, glutamate and aspartate. 2,3-Pyridine dicarboxylic acid (quinolinic acid) produced excitation of all cortical neurons tested. 2-Amino-5-phosphono-valeric acid, an NMDA antagonist, reduced responses to quinolinate, implying that this compound can act at NMDA receptors. Quinolinic acid may be of physiological interest as a potential endogenous excitant in the nervous system, and cis-2,3-PDA and its N-methyl derivative may be of use in studies of receptor pharmacology and the identification of synaptic transmitters.