An analysis of the cortical and striatal involvement in dyskinesia induced in rats by intracerebral injection of GABA-transaminase inhibitors and picrotoxin.
Unilateral intrastriatal injection of various substances induces a characteristic dyskinetic syndrome in rats. These substances include picrotoxin as well as a series of irreversible GABA-transaminase inhibitors. Using the degree of enzyme inhibition in various brain areas as a measure of drug distribution following intrastriatal administration of gamma-acetylenic GABA and gamma-vinyl GABA, there was found considerable retrodiffusion via the needle tract to the overlying cortex. Topical application of gamma-acetylenic GABA and gamma-vinyl GABA to the cortical surface overlying the striatum produced a high incidence of identical dyskinesias without any evidence of diffusion of drugs to the striatum. The cortically induced movements could be duplicated by picrotoxin application to a defined cortical area. These findings suggest that interference with gabaergic function in the striatum is not necessary for the production of the dyskinetic syndrome and that this syndrome may be a cortically induced phenomenon.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors*; D000287:Administration, Topical; D000818:Animals; D001921:Brain / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology*; D003342:Corpus Striatum / Q000201:enzymology*; D004058:Diffusion; D004195:Disease Models, Animal; D004409:Dyskinesia, Drug-Induced / Q000201:enzymology*; D005968:Glutamate Decarboxylase / Q000037:antagonists & inhibitors; D006816:Huntington Disease / Q000378:metabolism; D007267:Injections; D008297:Male; D010852:Picrotoxin / Q000494:pharmacology*; D051381:Rats; D000637:Transaminases / Q000037:antagonists & inhibitors*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D000612:4-Aminobutyrate Transaminase; D005968:Glutamate Decarboxylase; D010852:Picrotoxin; D000637:Transaminases; D005680:gamma-Aminobutyric Acid