Titre du document / Document title

Effects of antipsychotic drugs on neurotoxicity, expression of fos-like protein and c-fos mRNA in the retrosplenial cortex after administration of dizocilpine

Auteur(s) / Author(s)

FUJIMURA M. ⁽¹⁾ ; HASHIMOTO K. ⁽¹⁾ ; YAMAGAMI K. ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Tokyo Laboratories, Pharmaceutical Research Division, Yoshitomi Pharmaceutical Industries, Ltd, Iruma, Saitama, JAPON

Résumé / Abstract

In this study, we examined the effect of clozapine, olanzapine, risperidone and haloperidol on the neuropathology (i.e. neuronal vacuolization) and the expression of Fos-like protein and c-fos mRNA in the retrosplenial cortex of female Sprague-Dawley rats induced by the NMDA receptor antagonist dizocilpine. Pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, blocked the neuronal vacuolization produced by dizocilpine (0.5 mg/kg. s.c.) in the rat retrosplenial cortex in a dose-dependent manner. Furthermore, pretreatment (15 min) with clozapine or olanzapine, but not risperidone or haloperidol, significantly attenuated the expression of Fos-like protein in the retrosplenial cortex induced by dizocilpine (0.5 mg/kg. s.c.) in a dose-dependent manner. The marked expression of c-fos mRNA in the rat retrosplenial cortex induced by the administration of dizocilpine (0.5 mg/kg. s.c.) was significantly attenuated by pretreatment (15 min) with clozapine (10 mg/kg) or olanzapine (10 mg/kg). hut not risperidone (10 mg/kg) or haloperidol (10 mg/kg). The present results suggest that pharmacologically relevant doses of clozapine or olanzapine, but not risperidone or haloperidol, block the neuropathological changes and the expression of Fos-like protein and c-fos mRNA in the rat retrosplenial cortex elicited by the administration of dizocilpine. It is possible that the blockade of dizocilpine-induced neuropathological changes by clozapine and olanzapine may he related to the unique antipsychotic actions of these drugs in schizophrenic patients, although this remains to he verified.

Revue / Journal Title

European journal of pharmacology   ISSN 0014-2999   CODEN EJPHAZ 

Source / Source

2000, vol. 398, n^o1, pp. 1-10 (1 p.1/4)

Langue / Language

Anglais

Editeur / Publisher

Elsevier, Amsterdam, PAYS-BAS  (1967) (Revue)

Mots-clés anglais / English Keywords

Clozapine ; Chemotherapy ; Prevention ; Olanzapine ; Toxicity ; Immediate early gene ; Risperidone ; Gene expression ; Haloperidol ; Dizocilpine ; Neuroleptic ; Psychotropic ; Antagonist ; NMDA receptor ; Rat ; Animal ; Cerebral cortex ; Nervous system diseases ; Butyrophenone derivatives ; Central nervous system disease ; Rodentia ; Mammalia ; Vertebrata ; Glutamate receptor ;

Mots-clés français / French Keywords

Clozapine ; Chimiothérapie ; Prévention ; Olanzapine ; Toxicité ; Gène immédiat précoce ; Rispéridone ; Expression génique ; Halopéridol ; Dizocilpine ; Neuroleptique ; Psychotrope ; Antagoniste ; Récepteur NMDA ; Rat ; Animal ; Cortex cérébral ; Système nerveux pathologie ; Butyrophénone dérivé ; Système nerveux central pathologie ; Gène c-fos ; Dibenzodiazépine ; Thiéno benzodiazépine dérivé ; Rodentia ; Mammalia ; Vertebrata ; Récepteur glutamate ;

Mots-clés espagnols / Spanish Keywords

Clozapina ; Quimioterapia ; Prevención ; Olanzapina ; Toxicidad ; Gen inmediato precoz ; Risperidona ; Expresión genética ; Haloperidol ; Dizocilpina ; Neuroléptico ; Psicotropo ; Antagonista ; Receptor NMDA ; Rata ; Animal ; Corteza cerebral ; Sistema nervioso patología ; Butirofenona derivado ; Sistema nervosio central patología ; Rodentia ; Mammalia ; Vertebrata ; Receptor glutámato ;

Localisation / Location

INIST-CNRS, Cote INIST : 13322, 35400008872773.0010