Excitatory amino acid antagonists attenuate the effects of cocaine on extracellular dopamine in the nucleus accumbens.
The effect of N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate excitatory amino acid antagonists on systemic cocaine-induced increases in extracellular dopamine was examined. The alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate receptor subtype antagonist, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and N-methyl-D-aspartate receptor antagonists, 2-amino-5-phosphonovalerate and dizocilpine, were infused via a microdialysis probe placed in the nucleus accumbens. The local infusion of 2-amino-5-phosphonovalerate (500 microM), dizocilpine (50 microM) and CNQX (100 microM), started 80 min before cocaine injection, significantly inhibited the cocaine-induced increase in extracellular dopamine. The CNQX blockade was dose-dependent with respect to both CNQX concentration infused and dose of cocaine administered. Simultaneous infusion of the two antagonists (500 microM 2-amino-5-phosphonovalerate and 100 microM CNQX) did not lead to further reductions in the effects of cocaine when compared to either antagonist alone. Our results suggest that both N-methyl-Daspartate and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate/kainate subtypes of excitatory amino acid antagonist receptors may contribute to the stimulatory effect of cocaine on extracellular dopamine in the nucleus accumbens.
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Department of Psychiatry, Yale University School of Medicine, Connecticut, USA.
Bradberry
C W
CW
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D003042:Cocaine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004347:Drug Interactions; D018846:Excitatory Amino Acids / Q000037:antagonists & inhibitors*; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors
D018846:Excitatory Amino Acids; D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D015763:2-Amino-5-phosphonovalerate; D003042:Cocaine; D004298:Dopamine