Enhancement of serotonergic neural activity contributes to cyclosporine-induced tremors in mice.
A single cyclosporine injection (50 mg/kg, i.p.) significantly enhanced harmine- but not oxotremorine-induced tremors in mice. This potentiation became more apparent when cyclosporine (50 mg/kg, i.p.) was administered once a day for seven days. These findings suggest an involvement of monoaminergic mechanisms in cyclosporine-induced tremors. The effects of cyclosporine were examined on the dynamics of noradrenaline, dopamine and serotonin in the mouse brain. Both single and repeated treatment with cyclosporine significantly facilitated the serotonin turnover as estimated from the probenecid-induced accumulation of 5-hydroxyindoleacetic acid, but either mode of treatment failed to change the contents of monoamines and their metabolites or the turnover of noradrenaline and dopamine. Therefore, the cyclosporine-enhanced activity of serotonin neurons may be interpreted as producing adverse central effects, including tremors.
Shuto
H
H
Department of Hospital Pharmacy, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Kataoka
Y
Y
Kanaya
A
A
Matsunaga
K
K
Sueyasu
M
M
Oishi
R
R
D000818:Animals; D015306:Biogenic Monoamines / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D016572:Cyclosporine / Q000008:administration & dosage / Q000494:pharmacology*; D006213:Hallucinogens / Q000494:pharmacology; D006247:Harmine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009046:Motor Neurons / Q000187:drug effects*; D018721:Muscarinic Agonists / Q000494:pharmacology; D010095:Oxotremorine / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology*; D014202:Tremor / Q000139:chemically induced*
D015306:Biogenic Monoamines; D006213:Hallucinogens; D007166:Immunosuppressive Agents; D018721:Muscarinic Agonists; D012701:Serotonin; D006247:Harmine; D010095:Oxotremorine; D016572:Cyclosporine