Impact of cyclosporine upon emotional and social behavior in mice.
BACKGROUND
Cyclosporine induces psychological side effects but its mechanisms of action remain to be elucidated.


METHODS
Mice were injected with cyclosporine (0, 10, 60 mg/kg intraperitoneal) and indexes of both anxiety-related and social behaviors were examined. Release of serotonin and dopamine in the prefrontal cortex was also investigated by microdialysis.


RESULTS
Intraperitoneal administration of cyclosporine increased cyclosporine concentrations in the blood and brains in mice. Cyclosporine administration at a higher-dose reduced motor activity, increased indexes of anxiety-related behavior, and decreased an index of social interaction. The administration reduced release of serotonin and dopamine in the prefrontal cortex. Clozapine administration abolished the reduced release of dopamine and partially restored the index of social behavior in cyclosporine-injected mice.


CONCLUSIONS
This in vivo model suggests that cyclosporine at a high dose induced hypo-function of the prefrontal cortex as a result of reduced release of serotonin and dopamine, increased anxiety-related behavior, and disturbed social behavior. Clozapine partially restored an index of social behavior. The present findings are pathologically relevant in patients who take cyclosporine.
Sato
Yuki
Y
Department of Anesthesiology, Jichi Medical University, Tochigi-ken, Japan.
Takayanagi
Yuki
Y
Onaka
Tatsushi
T
Kobayashi
Eiji
E
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D004644:Emotions / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D017551:Microdialysis; D023421:Models, Animal; D014018:Tissue Distribution
D007166:Immunosuppressive Agents; D016572:Cyclosporine