Dose-dependent protective effects of apomorphine against methamphetamine-induced nigrostriatal damage

(R)-Apomorphine is a non-selective dopamine (DA) agonist which is used in t he treatment of Parkinson's disease. In addition to symptomatic effects, ap omorphine exerts a neuroprotective activity in specific experimental models . For instance, apomorphine prevents experimental parkinsonism induced by t he neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Neuroprotection obtained with apomorphine does not seem to be related to its dopamine (DA) agonist properties. instead it appears to be grounded on the antioxidant a nd the free radical scavenging effects of the compound. In this study, we s ought to determine whether apomorphine protects against methamphetamine tox icity. We found that apomorphine (1: 5 and 10 mg/kg) dose-dependently prote cts against methamphetamine- (5 mg/kg X3, 2 h apart) induced striatal DA lo ss and reduction of tyrosine hydroxylase (TH) activity in the rat striatum. These protective effects are neither due to a decrease in the amount of st riatal methamphetamine nor to hypothermia as indicated by measurement of st riatal methamphetamine and body temperature at different time intervals aft er drug administration. The effects of apomorphine were neither opposite to , nor reversed by the DA antagonist haloperidol despite no decrease in body temperature was observed when apomorphine was given in combination with ha loperidol. The present data are in line with recent studies suggesting a DA receptor-independent neuroprotective effect of apomorphine on DA neurons a nd call for further studies aimed at evaluating potential neuroprotective e ffects of apomorphine in Parkinson's disease. (C) 2001 Elsevier Science B.V . All rights reserved.