Antipsychotic drugs prevent the motor hyperactivity induced by psychotomimetic MK-801 in zebrafish (Danio rerio).
Glutamate N-methyl-d-aspartate (NMDA) receptor antagonists, such as dizocilpine (MK-801), elicit schizophrenia-like symptoms in humans and a behavioral syndrome in rodents, characterized by hyperlocomotion and stereotyped actions, which is antagonized by antipsychotic drugs. Animal models of schizophrenia have been established and used for the development of new antipsychotic drugs. In this work we characterized the behavioral effects of MK-801 and investigated the effect of typical and atypical antipsychotic treatments on locomotor activity as well on the hyperlocomotion induced by MK-801 in zebrafish. MK-801 (20 microM) increased the locomotor behavior as measured by the number of line crossings, distance traveled, and the mean speed in the tank test after 15, 30, and 60 min of exposure. All tested antipsychotics counteracted MK-801-induced hyperactivity on all parameters analyzed and at doses that, given alone, had no effect on spontaneous locomotor activity. The results suggest a similar profile between typical and atypical antipsychotics in the reversal of locomotor disorders induced by MK-801. Moreover, an anxiolytic effect was verified at 30 and 60 min of MK-801 exposure, which was not reversed by antipsychotics tested in this work. In addition, olanzapine, which alone caused an anxiolytic response, when given with MK-801 potentiated the latter's effect on anxiety. In this work we demonstrated the value of the zebrafish, a simple to use animal model, in developing some behavioral features observed in schizophrenia, which may indicate a new approach for drug screening.
Seibt
Kelly Juliana
KJ
Neurochemistry and Psychopharmacology Laboratory, Department of Molecular and Cellular Biology, Faculty of Biosciences, Pontifical Catholic University of Rio Grande do Sul, Avenida Ipiranga, 6681, 90619-900 Porto Alegre, RS, Brazil.
Oliveira
Renata da Luz
Rda L
Zimmermann
Fernanda Francine
FF
Capiotti
Katiúcia Marques
KM
Bogo
Maurício Reis
MR
Ghisleni
Gabriele
G
Bonan
Carla Denise
CD
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D016291:Dizocilpine Maleate / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D006213:Hallucinogens / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D006948:Hyperkinesis / Q000139:chemically induced / Q000517:prevention & control*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D015027:Zebrafish
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D006213:Hallucinogens; D016291:Dizocilpine Maleate