domoic-acid and selfotel

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.

Topics: alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; Animals; Corpus Striatum; Dizocilpine Maleate; Dopamine; Electric Stimulation; Kainic Acid; Ketamine; Male; N-Methylaspartate; Neuromuscular Depolarizing Agents; Neurons, Afferent; Pipecolic Acids; Quinoxalines; Rats; Rats, Sprague-Dawley