Effects of acute and chronic administration of cyclosporine on dopamine metabolism in the rat cochlea.
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.
Esquifino
A I
AI
Departamentos de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense de Madrid, Spain.
Arce
A
A
Vicente-Torres
M A
MA
Gil-Loyzaga
P E
PE
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
D007166:Immunosuppressive Agents; D015102:3,4-Dihydroxyphenylacetic Acid; D016572:Cyclosporine; D004298:Dopamine; D006719:Homovanillic Acid