Effects of olanzapine, fluoxetine and olanzapine/fluoxetine on creatine kinase activity in rat brain.
Recently, a fixed combination of the atypical antipsychotic olanzapine and the serotonin selective reuptake inhibitor (SSRI) fluoxetine has been approved in the US for the treatment of bipolar I depression. In this work, we evaluated the effect of acute and chronic administration of fluoxetine, olanzapine and the combination of fluoxetine/olanzapine on creatine kinase (CK) activity in the brain of rats. For acute treatment, adult male Wistar rats received one single injection of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg). For chronic treatment, adult male Wistar rats received daily injections of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25mg/kg) for 28 days. In the present study we observed that acute administration of OLZ inhibited CK activity in cerebellum and prefrontal cortex. The acute administration of FLX inhibited creatine kinase in cerebellum, prefrontal cortex, hippocampus, striatum and cerebral cortex. In the chronic treatment, when the animals were killed 2h after the last injection a decrease in creatine kinase activity after FLX administration, alone or in combination with OLZ, in cerebellum, prefrontal cortex, hippocampus, striatum and cerebral cortex of rats occurred. However, when the animals were killed 24h after the last injection, we found no alterations in the enzyme. Although it is difficult to extrapolate our findings to the human condition, the inhibition of creatine kinase activity by these drugs may be associated to the occurrence of some side effects of OLZ and FLX.
Agostinho
Fabiano R
FR
Laboratório de Neurociências, Programa de Pós-graduação em Ciências da Saúde, Universidade do Extremo Sul Catarinense, 88806-000 Criciúma, SC, Brazil.
Scaini
Giselli
G
Ferreira
Gabriela K
GK
Jeremias
Isabela C
IC
Réus
Gislaine Z
GZ
Rezin
Gislaine T
GT
Castro
Adalberto A
AA
Zugno
Alexandra I
AI
Quevedo
João
J
Streck
Emilio L
EL
D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001569:Benzodiazepines / Q000008:administration & dosage / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D052276:Creatine Kinase, BB Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D005473:Fluoxetine / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D000077152:Olanzapine; D051381:Rats; D017208:Rats, Wistar; D017367:Selective Serotonin Reuptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*
D014150:Antipsychotic Agents; D001569:Benzodiazepines; D052276:Creatine Kinase, BB Form; D005473:Fluoxetine; D000077152:Olanzapine; D017367:Selective Serotonin Reuptake Inhibitors