TY - JOUR
T1 - Effect of chronic angiotensin-converting enzyme inhibition on striatal dopamine content in the MPTP-treated mouse
AU - Jenkins, Trisha A.
AU - Wong, John Y.F.
AU - Howells, David W.
AU - Mendelsohn, Frederick A.O.
AU - Chai, Siew Yeen
PY - 1999/7/1
Y1 - 1999/7/1
N2 - We have previously shown that chronic treatment with the angiotensin- converting enzyme inhibitor perindopril increased striatal dopamine levels by 2.5-fold in normal Sprague-Dawley rats, possibly via modulation of the striatal opioid or tachykinin levels. In the present study, we investigated if this 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. C57BL/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 D2 receptor levels compared with control untreated mice. The dopamine content returned to control levels, and the increase in dopamine D2 receptor levels 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-converting enzyme inhibitor was administered (5 mg/kg/day for 7 days) immediately after the cessation of the MPTP treatment, there was no reversal of the effect of the neurotoxin in decreasing striatal dopamine content. Our results demonstrate that perindopril is an effective agent in increasing striatal dopamine content in an animal model of Parkinson's disease.
AB - We have previously shown that chronic treatment with the angiotensin- converting enzyme inhibitor perindopril increased striatal dopamine levels by 2.5-fold in normal Sprague-Dawley rats, possibly via modulation of the striatal opioid or tachykinin levels. In the present study, we investigated if this 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. C57BL/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 D2 receptor levels compared with control untreated mice. The dopamine content returned to control levels, and the increase in dopamine D2 receptor levels 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-converting enzyme inhibitor was administered (5 mg/kg/day for 7 days) immediately after the cessation of the MPTP treatment, there was no reversal of the effect of the neurotoxin in decreasing striatal dopamine content. Our results demonstrate that perindopril is an effective agent in increasing striatal dopamine content in an animal model of Parkinson's disease.
KW - Angiotensin-converting enzyme inhibitor
KW - Parkinson's disease
KW - Striatum
UR - http://www.scopus.com/inward/record.url?scp=0033038787&partnerID=8YFLogxK
U2 - 10.1046/j.1471-4159.1999.0730214.x
DO - 10.1046/j.1471-4159.1999.0730214.x
M3 - Article
C2 - 10386973
AN - SCOPUS:0033038787
SN - 0022-3042
VL - 73
SP - 214
EP - 219
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
IS - 1
ER -