Effect of chronic angiotensin-converting enzyme inhibition on striatal dopamine content in the MPTP-treated mouse

We have previously shown that chronic treatment with the angiotensin-conver ting enzyme inhibitor perindopril increased striatal dopamine levels by 2.5 -fold in normal Sprague-Dawley rats, possibly via modulation of the striata l opioid or tachykinin levels. In the present study, we investigated if thi s effect of perindopril persists in an animal model of Parkinson's disease, the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mouse, C57 BL/6 mice were treated with the neurotoxin (30 mg/kg/day intraperitoneally) for 4 days and then left for 3 weeks to allow the degeneration of striatal dopaminergic terminals. At this time, the mice exhibited a 40% decrease in striatal dopamine content and an accompanying 46% increase in dopamine D-2 receptor levels compared with control untreated mice. The dopamine content returned to control levels, and the increase in dopamine D-2 receptor leve ls was attenuated in mice treated with perindopril (5 mg/kg/day orally for 7 days) 2 weeks after the last dose of MPTP. When the angiotensin-convertin g enzyme inhibitor was administered (5 mg/kg/day for 7 days) immediately af ter the cessation of the MPTP treatment, there was no reversal of the effec t of the neurotoxin in decreasing striatal dopamine content. Our results de monstrate that perindopril is an effective agent in increasing striatal dop amine content in an animal model of Parkinson's disease.