Effects of acute and chronic administration of cyclosporine on dopamine metabolism in the rat cochlea

The effect of cyclosporine (CBA) on dopamine (DA) metabolism at the cochlea r level was analyzed. Adult male rats were submitted to CyA treatment at th e doses of 1, 5 or 20 mg/Kg/day, for 1 day (acute) or 8 days (chronic). Coc hlear contents of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (D OPAC) and homovanillic acid (HVA), were measured by using high performance liquid chromatography (HPLC-ED). Either dose of acutely administered CyA di d not modify cochlear DA content and markedly reduced that of DOPAC, in a n on dose-dependent way. Acute administration of 5 mg/Kg of CyA decreased HVA content while the highest dose increased it. DOPAC/DA index was significan tly reduced with either CyA dose, although HVA/DA index was not modified. C hronic treatment with CBA markedly reduced cochlear DA and DOPAC contents i n a non dose-dependent way. However, HVA content decreased after the highes t administration dose of the drug. DOPAC/DA index was further reduced after the drug chronic administration. An increased HVA/DA index was surprisingl y observed, after chronic administration of either dose of the drug, the re sponse being dose- dependent. These data show that acute treatment with CBA mainly affects the DA reuptake, while chronic treatment affected both DA r euptake and metabolism at the cochlear level.