European Journal of Pharmacology 1980-04-04

An analysis of the cortical and striatal involvement in dyskinesia induced in rats by intracerebral injection of GABA-transaminase inhibitors and picrotoxin.

M M Robin, M G Palfreyman, M M Zraika, P J Schechter

Index: Eur. J. Pharmacol. 62 , 319, (1980)

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Abstract

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.


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