title: Effects of acute and chronic administration of cyclosporine on dopamine metabolism in the rat cochlea.
abstract: The effect of cyclosporine (CyA) on dopamine (DA) metabolism at the cochlear level was analyzed. Adult male rats were submitted to CyA treatment at the doses of 1, 5 or 20 mg/Kg/day, for 1 day (acute) or 8 days (chronic). Cochlear contents of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), were measured by using high performance liquid chromatography (HPLC-ED). Either dose of acutely administered CyA did not modify cochlear DA content and markedly reduced that of DOPAC, in a non dose-dependent way. Acute administration of 5 mg/Kg of CyA decreased HVA content while the highest dose increased it. DOPAC/DA index was significantly reduced with either CyA dose, although HVA/DA index was not modified. Chronic treatment with CyA markedly reduced cochlear DA and DOPAC contents in a non dose-dependent way. However, HVA content decreased after the highest administration dose of the drug. DOPAC/DA index was further reduced after the drug chronic administration. An increased HVA/DA index was surprisingly observed, after chronic administration of either dose of the drug, the response being dose- dependent. These data show that acute treatment with CyA mainly affects the DA reuptake, while chronic treatment affected both DA reuptake and metabolism at the cochlear level.
authors.affiliation: Departamentos de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
authors.forename: A I
authors.initials: AI
authors.lastname: Esquifino
authors.forename: A
authors.initials: A
authors.lastname: Arce
authors.forename: M A
authors.initials: MA
authors.lastname: Vicente-Torres
authors.forename: P E
authors.initials: PE
authors.lastname: Gil-Loyzaga
mesh_terms: D015102:3,4-Dihydroxyphenylacetic Acid / Q000032:analysis / Q000378:metabolism; D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism*; D016572:Cyclosporine / Q000008:administration & dosage*; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006719:Homovanillic Acid / Q000032:analysis / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D017208:Rats, Wistar
chemical_list: D007166:Immunosuppressive Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D016572:Cyclosporine; D004298:Dopamine; D006719:Homovanillic Acid