Evaluation of the mechanisms underlying the kainate-induced impairment of [3H]dopamine release in the rat striatum.
Kainic acid caused a marked decrease of the electrically evoked release of [3H]dopamine from rat striatal slices 4 days after its injection (10 nmol/microliters) into the corpus striatum. This damage was prevented by the non-N-methyl-D-aspartate (non-NMDA) receptor antagonist 6,7-dinitroquinoxaline-2,3-dione (DNQX) when co-injected with kainic acid into the striatum. Prior systemic administration of the NMDA selective antagonists (cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS 19755), dizocilpine (MK-801) and ketamine did not alter the kainate effect. Previous destruction of the cortico-striatal pathway abolished the kainate-induced decrease of [3H]dopamine release. When injected into the striatum, domoic acid or alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) mimicked kainic acid and damaged the dopaminergic nigro-striatal afferents. The [3H]dopamine release evoked by electrical stimulation of slices of frontal cortex was unaffected following local injections of kainic acid. Taken together, the results indicate that AMPA/kainate receptors play a key role in the impairment of [3H]dopamine release caused by kainate in the striatum. However, the kainic acid effect is probably indirect since it appears to require the availability of endogenous glutamate originating from cortico-striatal afferents.
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Institute of Pharmacology and Pharmacognosy, University of Genova, Italy.
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D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism*; D004558:Electric Stimulation; D007608:Kainic Acid / Q000031:analogs & derivatives / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology; D008297:Male; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors; D009467:Neuromuscular Depolarizing Agents / Q000494:pharmacology; D009475:Neurons, Afferent / Q000187:drug effects; D010875:Pipecolic Acids / Q000494:pharmacology; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000494:pharmacology
D009467:Neuromuscular Depolarizing Agents; D010875:Pipecolic Acids; D011810:Quinoxalines; C053672:selfotel; C056723:FG 9041; D016202:N-Methylaspartate; D007649:Ketamine; D016291:Dizocilpine Maleate; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; C012301:domoic acid; D007608:Kainic Acid; D004298:Dopamine