Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice.

AIM

Aripiprazole is an antipsychotic agent to treat schizophrenia, which acts through dopamine D(2) partial agonism, serotonin 5-HT(1A) partial agonism and 5-HT(2A) antagonism. This study was designed to evaluate the neurobehavioral effects and genotoxic/mutagenic activities of the agent, as well as its effects on lipoperoxidation.

METHODS

Open field and inhibitory avoidance tasks were used. Thirty min before performing the behavioral tasks, adult male CF-1 mice were administered aripiprazole (1, 3 or 10 mg/kg, ip) once for the acute treatment, or the same doses for 5 d for the subchronic treatment. Genotoxic effects were assessed using comet assay in the blood and brain tissues. Mutagenic effects were evaluated using bone marrow micronucleus test. Lipoperoxidation was assessed with thiobarbituric acid reactive substances (TBARS).

RESULTS

Acute and subchronic treatments significantly decreased the number of crossing and rearing in the open field task. Acute treatment significantly increased the step-down latency for both the short- and long-term memory in the inhibitory avoidance task. Subchronic treatments with aripiprazole (3 and 10 mg/kg) caused significant DNA strain-break damage in peripheral blood but not in the brain. Mutagenic effect was not detected in the acute and subchronic treatments. Nor TBARS levels in the liver were affected.

CONCLUSION

Aripiprazole improved memory, but could impair motor activities in mice. The drug increased DNA damage in blood, but did not show mutagenic effects, suggesting that it might affect long-term genomic stability.