Alpha-methyl-para-tyrosine pretreatment protects from striatal neuronal death induced by four-vessel occlusion in the rat.
Rats were treated with alpha-methyl-para-tyrosine (AMT, 250 mg/kg, i.p), an hydroxylase inhibitor, in order to decrease brain levels of catecholamines. Six hours later, when cerebral dopamine (DA) and norepinephrine were reduced by about 80%, a transient forebrain ischemia of 30 min duration was induced by four-vessel occlusion technique. Evaluation of brain damage 72 hours after ischemia showed that AMT treatment significantly decreased neuronal necrosis in the striatum but had no cytoprotective effect in the CA1 sector of the hippocampus and in the neocortex. AMT treatment reduced mortality within the ischemic period but did not affect either the mortality within the recirculation period or the postischemic neurologic deficit. These results suggest that the striatal cytoprotective effect of AMT is linked to cerebral DA depletion and that excessive release of DA during ischemia or dopaminergic hyperactivity during recirculation play a detrimental role in the development of ischemic cell damage in the striatum.
Marie
C
C
Laboratoire de Pharmacodynamie et de Physiologie Pharmaceutique, Faculté de Pharmacie, Dijon, France.
Mossiat
C
C
Beley
A
A
Bralet
J
J
D000818:Animals; D001921:Brain / Q000378:metabolism; D002395:Catecholamines / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008781:Methyltyrosines / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects*; D016548:Prosencephalon / Q000098:blood supply; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014446:Tyrosine 3-Monooxygenase / Q000037:antagonists & inhibitors*; D019805:alpha-Methyltyrosine
D002395:Catecholamines; D008781:Methyltyrosines; D019805:alpha-Methyltyrosine; D014446:Tyrosine 3-Monooxygenase