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.
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.
Authors: Suellen Almeida-Corrêa; Thiago C Moulin; Clarissa F D Carneiro; Marina M C Gonçalves; Lara S Junqueira; Olavo B Amaral Journal: Learn Mem Date: 2015-02-17 Impact factor: 2.460
Authors: Jan Brosda; Thorsten Becker; Mathis Richter; Marie Jakobs; Tina Hörbelt; Ivo Bendix; Laura Lückemann; Manfred Schedlowski; Martin Hadamitzky Journal: Psychopharmacology (Berl) Date: 2020-12-21 Impact factor: 4.530
Authors: R Barzilay; T Ben-Zur; O Sadan; Z Bren; M Taler; N Lev; I Tarasenko; R Uzan; I Gil-Ad; E Melamed; A Weizman; D Offen Journal: Transl Psychiatry Date: 2011-12-13 Impact factor: 6.222