title: Time-dependent striatal dopamine depletion after injection of 6-hydroxydopamine in the rat. Comparison of single bilateral and double bilateral lesions.
abstract: For future investigation of possible perturbation of circadian rhythm in animal models of Parkinson's disease we needed an animal model providing lasting 80-100% striatal dopaminergic depletion in rats, but without induced mortality. We have thus compared the effects of a single hydroxydopamine bilateral striatal lesion (SB-hydroxydopamine) with those of a double hydroxydopamine bilateral lesion (DB-hydroxydopamine) at the same dose (16 microg/striatum) by HPLC determination of dopamine and 3,4-dihydrophenylacetic acid (dopac) levels in the striatum. Two weeks after neurosurgery, SB-hydroxydopamine and DB-hydroxydopamine induced dopaminergic depletion of at least 81% compared with control groups. After eight weeks striatal dopaminergic depletion was only 60.97% in SB-hydroxydopamine rats, suggesting a compensatory phenomenon, whereas in DB-hydroxydopamine rats dopaminergic loss was stable at 88%. For the DB-hydroxydopamine group the dopac/dopamine ratio was significantly increased at week 2 only, whereas no significant change was observed for other groups. This increase might be explained by increased dopamine turnover. We have demonstrated that striatal DB-hydroxydopamine injection induces lasting 80-100% neuronal loss, close to that observed in the disease in man, without induced mortality, and provides a tool which meets our experimental requirements.
authors.affiliation: Department of Medical and Clinical Pharmacology, Faculty of Medicine, Marseille, France.
authors.forename: V
authors.initials: V
authors.lastname: Ben
authors.forename: O
authors.initials: O
authors.lastname: Blin
authors.forename: B
authors.initials: B
authors.lastname: Bruguerolle
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D007839:Functional Laterality; D007267:Injections; D008297:Male; D016627:Oxidopamine / Q000008:administration & dosage / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015102:3,4-Dihydroxyphenylacetic Acid; D016627:Oxidopamine; D004298:Dopamine