Neuroprotective effects mediated by dopamine receptor agonists against malonate-induced lesion in the rat striatum.
In rats, intrastriatal injection of malonate, a reversible inhibitor of the mitochondrial enzyme succinate dehydrogenase, induces a lesion similar to that observed following focal ischemia or in Huntington's disease. In this study we used the malonate model to explore the neuroprotective potential of dopamine agonists. Rats were injected intraperitoneally with increasing concentrations of D1, D2, or mixed D1/D2 dopamine agonists prior to intrastriatal injection of malonate. Administration of increasing doses of the D2-specific agonist quinpirole resulted in increased protection against malonate toxicity. Conversely, the D1-specific agonist SKF-38393, as well as the mixed D1/D2 agonist apomorphine, conferred higher neuroprotection at lower than at higher drug concentrations. Our data suggest that malonate- induced striatal toxicity can be attenuated by systemic administration of dopamine agonists, with D1 and D2 agonists showing different profiles of efficacy.
Laboratory of Functional Neurochemistry, IRCCS C. Mondino, Pavia, Italy.
R
R
Fancellu
M-T
MT
Armentero
G
G
Nappi
F
F
Blandini
D000704:Analysis of Variance; D000818:Animals; D003342:Corpus Striatum / Q000473:pathology*; D004195:Disease Models, Animal; D018491:Dopamine Agonists / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D003576:Electron Transport Complex IV / Q000378:metabolism; D007511:Ischemia / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D008314:Malonates; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley
D018491:Dopamine Agonists; D004338:Drug Combinations; D008314:Malonates; D018696:Neuroprotective Agents; C030290:malonic acid; D003576:Electron Transport Complex IV