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

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 248; no. 2; pp. 722 - 728
• Main Authors: CLOW, D. W, JHAMANDAS, K
• Format: Journal Article
• Language: English
• Published: Bethesda, MD American Society for Pharmacology and Experimental Therapeutics 01.02.1989
• Subjects: 2-Amino-5-phosphonovalerate - analogs & derivatives; Amino Acids - pharmacology; Analytical, structural and metabolic biochemistry; Animals; Aspartic Acid - analogs & derivatives; Aspartic Acid - pharmacology; Biological and medical sciences; Caudate Nucleus - drug effects; Caudate Nucleus - secretion; Dopamine - secretion; Dose-Response Relationship, Drug; Fundamental and applied biological sciences. Psychology; Glutamates - pharmacology; Glutamic Acid; In Vitro Techniques; Magnesium - pharmacology; Male; N-Methylaspartate; Non peptidic neurotransmitters, polyamines; Other biological molecules; Oxadiazoles - pharmacology; Phenazocine - analogs & derivatives; Phenazocine - pharmacology; Potassium - pharmacology; Putamen - drug effects; Putamen - secretion; Quisqualic Acid; Rats; Rats, Inbred Strains; Receptors, N-Methyl-D-Aspartate; Receptors, Neurotransmitter - drug effects; Brain; Dopamine; Rat; Rodentia; HPLC chromatography; Glutamate; Metabolism; Putamen; Electrochemical detector; Vertebrata; Mammalia; Endogenous; Caudate nucleus; Biogenic amine; Excitatory aminoacid; Release
• ISSN: 0022-3565; 1521-0103

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.