Antagonism of the hypermotility response induced by excitatory amino acids in the rat nucleus accumbens

Abstract

Several compounds have been shown to antagonize the excitation of single neurons produced by excitatory amino acids. This study was designed to determine the effectiveness of these compounds in antagonizing the hypermotility response to excitatory amino acids after intraaccumbens administration. Of the putative antagonists tested, D-aminoadipic acid, diaminopimelic acid and glutamic acid diethyl ester all showed significant inhibitory effects on excitatory amino acid-induced hypermotility while 2-amino-5-phosphonovaleric acid, γ-D-glutamylglycine, 2-amino-4-phosphonobutyric acid and cis-2,3-piperidine dicarboxylic acid were ineffective. D-Aminoadipic acid decreased N-methyl-aspartic acid-induced hypermotility while having no significant effect on the hypermotility responses induced by kainic or quisqualic acids. Diaminopimelic acid markedly decreased N-methyl-aspartic acid- and kainic acid-induced hypermotility but was totally ineffective on quisqualic acid-induced hypermotility. In contrast to D-aminoadipic acid, glutamic acid diethyl ester antagonized the increase in motility produced by kainic and quisqualic acids but not that produced by N-methyl-aspartic acid. The above data suggests that N-methyl-aspartic acid and quisqualic acid may produce their motor effects through the activation of two different receptors in the nucleus accumbens while kainic acid may mediate its hypermotility response through both N-methyl-aspartic acid and quisqualic acid receptors. However, a third receptor type activated solely by kainic acid cannot be excluded at this time.