ENHANCEMENT OF SEROTONERGIC NEURAL ACTIVITY CONTRIBUTES TO CYCLOSPORINE-INDUCED TREMORS IN MICE

A single cyclosporine injection (50 mg/kg, i.p.) significantly enhance d harmine but not oxotremorine-induced tremors in mice. This potentiat ion became more apparent when cyclosporine (50 mg/kg, i.p.) was admini stered once a day for seven days. These findings suggest an involvemen t of monoaminergic mechanisms in cyclosporine-induced tremors. The eff ects of cyclosporine were examined on the dynamics of noradrenaline, d opamine and serotonin in the mouse brain. Both single and repeated tre atment with cyclosporine significantly facilitated the serotonin turno ver as estimated from the probenecid-induced accumulation of 5-hydroxy indoleacetic acid, but either mode of treatment failed to change the c ontents of monoamines and their metabolites or the turnover of noradre naline and dopamine. Therefore thr cyclosporine-enhanced activity of s erotonin neurons may be interpreted as producing adverse central effec ts, including tremors. (C) 1998 Elsevier Science B.V.