Effects of olanzapine, fluoxetine and olanzapine/fluoxetine on creatine kinase activity in rat brain
Effects of olanzapine, fluoxetine and olanzapine/fluoxetine on creatine kinase activity in rat brain
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DOI：
10.1016/j.brainresbull.2009.09.002
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发表时间：
2009-12-16
影响因子：
3.8
通讯作者：
Streck, Emilio L.
中科院分区：
文献类型：
--
作者：
Agostinho, Fabiano R.;Scaini, Giselli;Streck, Emilio L.
最近，非典型抗精神病药物奥氮平和血清素选择性再摄取抑制剂（SSRI）氟西汀的固定组合在美国被批准用于治疗双相I型抑郁症。在这项工作中，我们评估了急性和慢性给药氟西汀、奥氮平和氟西汀/奥氮平联合给药对大鼠大脑肌酸激酶（CK）活性的影响。对于急性治疗，成年雄性Wistar大鼠单次注射奥氮平（3或6 mg/kg）和/或氟西汀（12.5或25 mg/kg）。对于慢性治疗，成年雄性Wistar大鼠每天注射奥氮平（3或6 mg/kg）和/或氟西汀（12.5或25 mg/kg），持续28天。在本研究中，我们观察到急性给药OLZ抑制小脑和前额皮质CK活性。急性给药FLX可抑制小脑、前额皮质、海马、纹状体和大脑皮质的肌酸激酶。慢性给药组，末次给药后2h处死大鼠，单用或联用OLZ后，大鼠小脑、前额叶皮层、海马、纹状体、大脑皮层肌酸激酶活性下降。然而，当动物在最后一次注射后24小时被杀死时，我们发现酶没有变化。虽然很难将我们的发现推断到人类的情况，但这些药物对肌酸激酶活性的抑制可能与OLZ和FIX的一些副作用的发生有关。(C) 2009爱思唯尔公司版权所有。
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 25 mg/kg). For chronic treatment, adult male Wistar rats received daily injections of olanzapine (3 or 6 mg/kg) and/or fluoxetine (12.5 or 25 mg/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 2 h 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 24 h 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 FIX. (C) 2009 Elsevier Inc. All rights reserved.