title: Neurobehavioral and genotoxic parameters of antipsychotic agent aripiprazole in mice.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratório de Genética Toxicológica, Programa de Pós-Graduação em Genética e Toxicologia Aplicada, Universidade Luterana do Brasil, ULBRA, Bairro São José, Canoas, RS, Brazil. jnpicada@cpovo.net
authors.forename: Jaqueline Nascimento
authors.initials: JN
authors.lastname: Picada
authors.forename: Bruna de Jesus Neto
authors.initials: Bde J
authors.lastname: Dos Santos
authors.forename: Franciele
authors.initials: F
authors.lastname: Celso
authors.forename: Jéssica Dias
authors.initials: JD
authors.lastname: Monteiro
authors.forename: Kelly Morais
authors.initials: KM
authors.lastname: Da Rosa
authors.forename: Leandro Rosa
authors.initials: LR
authors.lastname: Camacho
authors.forename: Luciana Rodrigues
authors.initials: LR
authors.lastname: Vieira
authors.forename: Taís Madelon
authors.initials: TM
authors.lastname: Freitas
authors.forename: Tatiana Grasiela
authors.initials: TG
authors.lastname: Da Silva
authors.forename: Viviane Minuzzo
authors.initials: VM
authors.lastname: Pontes
authors.forename: Patrícia
authors.initials: P
authors.lastname: Pereira
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D020552:Comet Assay; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D015162:Micronucleus Tests; D009153:Mutagens / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D012559:Schizophrenia / Q000188:drug therapy
chemical_list: D014150:Antipsychotic Agents; D009153:Mutagens; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole