title: Antipsychotic drugs reverse MK-801-induced cognitive and social interaction deficits in zebrafish (Danio rerio).
abstract: Schizophrenia is a severe mental illness characterized by positive and negative symptoms and cognitive deficits. Reduction of glutamatergic neurotransmission by NMDA receptor antagonists mimics symptoms of schizophrenia. Modeling social interaction and cognitive impairment in animals can be of great benefit in the effort to develop novel treatments for negative and cognitive symptoms of schizophrenia. Studies have demonstrated that these behavioral changes are, in some cases, sensitive to remediation by antipsychotic drugs. The zebrafish has been proposed as a candidate to study the in vivo effects of several drugs and to discover new pharmacological targets. In the current study we investigated the ability of antipsychotic drugs to reverse schizophrenia-like symptoms produced by the NMDA receptor antagonist MK-801. Results showed that MK-801 (5μM) given pre-training hindered memory formation while both atypical antipsychotics sulpiride (250μM) and olanzapine (50μM) improved MK-801-induced amnesia. The same change was observed in the social interaction task, where atypical antipsychotics reversed the MK-801-induced social interaction deficit whereas the typical antipsychotic haloperidol (9μM) was ineffective to reverse those behavioral deficits. Therefore, MK-801-treated zebrafish showed some behavioral features observed in schizophrenia, such as cognitive and social interaction deficits, which were reverted by current available atypical drugs.
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Departamento de Biologia Celular e Molecular, Programa de Pós-Graduação em Biologia Celular e Molecular. Faculdade de Biociências, Pontifícia Universidade Católica do Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900, Porto Alegre, RS, Brazil.
authors.forename: Kelly Juliana
authors.initials: KJ
authors.lastname: Seibt
authors.forename: Angelo Luis
authors.initials: AL
authors.lastname: Piato
authors.forename: Renata
authors.initials: R
authors.lastname: da Luz Oliveira
authors.forename: Katiucia Marques
authors.initials: KM
authors.lastname: Capiotti
authors.forename: Monica Ryff
authors.initials: MR
authors.lastname: Vianna
authors.forename: Carla Denise
authors.initials: CD
authors.lastname: Bonan
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D001362:Avoidance Learning / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects; D003072:Cognition Disorders / Q000139:chemically induced* / Q000188:drug therapy*; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000633:toxicity*; D004347:Drug Interactions; D007398:Interpersonal Relations; D008297:Male; D018709:Statistics, Nonparametric; D015027:Zebrafish
chemical_list: D014150:Antipsychotic Agents; D016291:Dizocilpine Maleate