Some factors influencing the neurotoxicity of intrastriatal injections of kainic acid.
Intrastriatal injections of kainic acid are known to destroy striatal neurons including many containing choline acetyltransferase (CAT) and glutamic acid decarboxylase (GAD). Using these enzymes as indices of neuronal loss, the neurotoxicity of small doses of kainic acid was found to be influenced by injection time and volume. It was partly blocked by coinjection of some but not all glutamate antagonists or by prior lesioning of the corticostriatal tract. Other adjuvants, drugs, or lesions tested had little modifying effect, except that changes in the dopaminergic system seemed to increase the toxicity towards cholinergic but not GABAnergic systems. High-affinity glutamate accumulation by neostriatal synaptosomes was significantly increased 1--7 days following kainic acid injections. MAO and acetylcholinesterase activities were depressed in kainic acid-lesioned striata but not nearly as much as were CAT and GAD. An indirect mechanism involving glutamate release and inhibition of reuptake is suggested for kainic acid neurotoxicity.
D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D001533:Belladonna Alkaloids / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects* / Q000502:physiology; D005968:Glutamate Decarboxylase / Q000378:metabolism; D005971:Glutamates / Q000378:metabolism; D005973:Glutamine / Q000494:pharmacology; D007267:Injections; D007608:Kainic Acid / Q000633:toxicity*; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000494:pharmacology; D011759:Pyrrolidines / Q000633:toxicity*; D051381:Rats; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001533:Belladonna Alkaloids; D005971:Glutamates; D018377:Neurotransmitter Agents; D011759:Pyrrolidines; D005973:Glutamine; D005680:gamma-Aminobutyric Acid; D008995:Monoamine Oxidase; D002795:Choline O-Acetyltransferase; D000110:Acetylcholinesterase; D005968:Glutamate Decarboxylase; D007608:Kainic Acid