Haloperidol and clozapine, but not olanzapine, induces oxidative stress in rat brain.
Typical and atypical antipsychotic drugs have been shown to have different clinical and behavioral profiles. Haloperidol (HAL) is a typical neuroleptic that acts primarily as a D2 dopamine receptor antagonist. It has been proposed that reactive oxygen species play a causative role in neurotoxic effects induced by HAL. We evaluated oxidative damage in rat brain induced by chronic HAL, clozapine (CLO) or olanzapine (OLZ) administration. Adult male Wistar rats received daily injections of Hal (1.5mg/kg), CLO (25mg/kg) or OLZ (2.5, 5.0 or 10.0mg/kg). Control animals were given saline (SAL; NaCl 0.9%). Thiobarbituric acid reactive substances (TBARS) and protein carbonylation were measured in the hippocampus (HP), striatum (ST) and cortex (CX). TBARS was increased in the striatum after HAL treatment. In contrast, there was a decrease of TBARS levels induced by HAL, CLO and OLZ treatments in the cortex. Protein carbonyls after HAL and CLO treatment was increased in the hippocampus, compared to control. In hippocampus, OLZ did not show significant difference to control in both oxidative parameters. Our findings demonstrated that atypical antipsychotic CLO produced less oxidative damage than HAL and we did not find oxidative damage induced by OLZ.
Reinke
Adalisa
A
Laboratório de Neurociências, Universidade do Extremo Sul Catarinense, Avenida Univeristaria, 1105, 88806-000 Criciúma, SC, Brazil.
Martins
Márcio Rodrigo
MR
Lima
Mauricio S
MS
Moreira
Jose Cláudio
JC
Dal-Pizzol
Felipe
F
Quevedo
João
J
D000818:Animals; D001569:Benzodiazepines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003024:Clozapine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D000077152:Olanzapine; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D001569:Benzodiazepines; D003024:Clozapine; D006220:Haloperidol; D000077152:Olanzapine