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Neuroprotective effects mediated bydopamine receptor agonists against malonate-induced lesion inthe rat striatum
Authors:R. Fancellu  M.-T. Armentero  G. Nappi  F. Blandini
Affiliation:(1) Laboratory of Functional Neurochemistry, IRCCS C. Mondino, Pavia, Italy;(2) University of Insubria, Varese, Italy;(3) Department of Neurology and Otorhinolaryngology, University of Rome "ldquo"La Sapienza"rdquo", Rome, Italy
Abstract:Abstract. In rats, intrastriatal injection of malonate, a reversibleinhibitor of the mitochondrial enzyme succinate dehydrogenase,induces a lesion similar to that observed following focalischemia or in Huntingtonrsquos disease. In this study we used themalonate model to explore the neuroprotective potential ofdopamine agonists. Rats were injected intraperitoneally withincreasing concentrations of D1,D2, or mixedD1/D2 dopamineagonists prior to intrastriatal injection of malonate.Administration of increasing doses of theD2-specific agonist quinpirole resultedin increased protection against malonate toxicity. Conversely,the D1-specific agonist SKF-38393, aswell as the mixedD1/D2 agonistapomorphine, conferred higher neuroprotection at lower than athigher drug concentrations. Our data suggest that malonate-induced striatal toxicity can be attenuated by systemicadministration of dopamine agonists, withD1 and D2 agonistsshowing different profiles of efficacy.
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