Typical and atypical antipsychotic drugs have different clinical and behavioural profiles. It is well described that inhibition of creatine kinase activity has been implicated in the pathogenesis of a number of diseases, especially in the brain. In this work, we evaluate the effect of haloperidol, clozapine, olanzapine or aripiprazole chronic administration on creatine kinase activity in brain of rats. Adult male Wistar rats received daily injections of haloperidol (1.5 mg/kg), clozapine (25 mg/kg), olanzapine (2.5, 5 or 10 mg/kg) or aripiprazole (2, 10 or 20 mg/kg). Our results demonstrate that haloperidol did not affect the enzyme activity in brain of rats. Clozapine inhibited the enzyme activity only in cerebellum and prefrontal cortex of rats. Aripiprazole did not affect creatine kinase in hippocampus, cerebellum and prefrontal cortex. The administration of 2.0 mg/kg aripiprazole did not alter creatine kinase activity, but 10.0 and 20.0 mg/kg aripiprazole activated the enzyme in striatum and cerebral cortex. Finally, the higher dose of olanzapine (10.0 mg/kg) activated the enzyme in striatum of rats. In hippocampus and cerebral cortex, we could not verify any effect of olanzapine on creatine kinase activity. The inhibitory effect of clozapine and olanzapine on creatine kinase activity in cerebellum and prefrontal cortex suggest that these drugs may impair energy metabolism in these brain areas.Creatine kinase (EC 2.7.3.2) is a crucial enzyme for high energy-consuming tissues like brain, skeletal muscle and heart. This enzyme works as a buffering system of cellular ATP levels, playing a central role in energy metabolism. Creatine kinase catalyses the reversible transfer of the phosphoryl group from phosphocreatine to ADP, regenerating ATP [1][2][3]. It is also known that a decrease in creatine kinase activity is associated with neurodegenerative pathways that result in neuronal death in brain ischaemia [4], neurodegenerative diseases [5,6], bipolar disorder [7] and other pathological states [8,9].Brain and other high energy tissues are more susceptible to reduction of energy metabolism. In this context, neuropsychiatry disorders, such as schizophrenia, depression and bipolar disorder, have been related to dysfunction in brain metabolism [10,11]. The metabolism dysfunction includes mitochondrial impairment [12,13], increase in reactive oxygen species production and expression of biochemical markers of cellular degeneration [14 -16].The therapeutic efficacy of antipsychotic drugs is generally believed to be due to their ability to block central dopamine D 2 receptor [17,18]. The older generation of antipsychotics, known as typical antipsychotics, showed great promise to control acute positive symptomatology and the induction of extrapyramidal side effects, which often lead to persistent tardive dyskinesia and termination of treatment, limiting the long-term use of these agents. In addition, the long-term use of typical antipsychotics was often found to be associated with increased core negative sympto...
