Characterization of L-glutamate action on the release of endogenous dopamine from the rat caudate-putamen

DW Clow and K Jhamandas

Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

In the present study the effect of L-glutamic acid (L-Glu), N-methyl-D- aspartic acid (NMDA), kainic acid (KA) and quisqualic acid (QUIS) on the release of endogenous dopamine (DA) from slices of the rat caudate- putamen was investigated. DA was measured by high-performance liquid chromatography coupled to an electrochemical detector. L-Glu, NMDA, KA and QUIS, in the absence of Mg++, produced a dose-related, Ca++- dependent increase in DA release. The order of agonist efficacy was L- Glu greater than NMDA greater than KA = QUIS. D-2-amino-7- phosphonoheptanoic acid (0.5 mM), but not L-2-amino-7- phosphonoheptanoic acid, antagonized the action of L-Glu and NMDA, but did not modify the effect of KA or QUIS. Tetrodotoxin (0.1 microM) partially inhibited the stimulatory effect of KA and QUIS, but not that of L-Glu or NMDA. Mg++ (1.2 mM) abolished the excitatory effect of NMDA, significantly reduced the action of L-Glu, but did not influence the action of KA or QUIS. The inhibitory action of Mg++ on the L-Glu- induced DA release was reversed when L-Glu was coupled to high concentrations of K+. N-allylnormetazocine (SKF-10,047), a benzmorphan agent, produced a stereospecific inhibition of L-Glu-induced DA release. This inhibition was also produced by 1-[1-(2- thienyl)cyclohexyl]piperidine, a phencyclidine receptor ligand, but not by 1,3-di-O-tolylguanidine, a sigma receptor-selective ligand. The results of this study show that L-Glu increases DA release predominantly by activation of the NMDA receptor located presynaptically on dopaminergic afferents.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 248, Issue 2, pp. 722-728, 02/01/1989
Copyright © 1989 by American Society for Pharmacology and Experimental Therapeutics