Effects of kainic acid, quisqualic acid, and their antagonist, pCB-PzDA, on rat electrocorticograms and monoamine metabolite levels in rat striatum.

Abstract

The action of kainic acid (KA), quisqualic acid (QA), and 1-(4-chlorobenzoyl)-piperazine-2,3-dicarboxylic acid (pCB-PzDA) was investigated in the central nervous system of male Sprague Dawley rats. Intracerebroventricularly injected KA and QA (100 nmol) induced spike discharges, and pCB-PzDA (100 nmol) suppressed electrocorticograms for one hour. pCB-PzDA enhanced the KA-induced spike discharges and inhibited those induced by QA. 2,3-Di-hydroxyphenylacetic acid(DOPAC) and homovanillic acid (HVA) levels were increased transiently by 10 nmol and continuously by 100 nmol of KA. KA dose-dependently increased 5-hydroxyindoleacetic acid (5-HIAA) levels 2 hours after administration. While 10 nmol of QA slightly increased the HVA level, 100 nmol of QA significantly increased DOPAC, HVA, and 5-HIAA levels. DOPAC and HVA levels were increased by 100 nmol of pCB-PzDA, although this agent inhibited KA-induced increases in DOPAC, HVA, and 5-HIAA levels. On the other hand, while pCB-PzDA first inhibited QA-induced increases in DOPAC, HVA and 5-HIAA levels for one hour, DOPAC and HVA levels thereafter increased additively. These findings suggest that pCB-PzDA may act not only as a NMDA antagonist, but that it may also act directly on dopaminergic neurons.