Titre
An animal model with relevance to schizophrenia: sex-dependent cognitive deficits in osteogenic disorder-Shionogi rats induced by glutathione synthesis and dopamine uptake inhibition during development
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Castagné, Vincent
Auteure/Auteur
Cuénod, Michel
Auteure/Auteur
Do Kim, Quang
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0306-4522
Statut éditorial
Publié
Date de publication
2004
Volume
123
Numéro
4
Première page
821
Dernière page/numéro d’article
834
Peer-reviewed
Oui
Langue
anglais
Notes
DA - 20040130 IS - 0306-4522 LA - eng PT - Journal Article RN - 0 (Dopamine Uptake Inhibitors) RN - 0 (Enzyme Inhibitors) RN - 0 (Piperazines) RN - 5072-26-4 (Buthionine Sulfoximine) RN - 51-61-6 (Dopamine) RN - 67469-78-7 (vanoxerine) RN - 70-18-8 (Glutathione) SB - IM Institution : Center for Research in Psychiatric Neuroscience, Department of Adult Psychiatry, Lausanne University-CHUV, Site de Cery, CH-1008 Prilly-Lausanne, Switzerland. vincent.castagne@inst.hospvd.ch Mention de responsabiblité : Castagne,V.;Cuenod,M.;Do,K.Q. SAPHIRID:48090
Résumé
Low glutathione levels have been observed in the prefrontal cortex and the cerebrospinal fluid of schizophrenic patients, possibly enhancing the cerebral susceptibility to oxidative stress. We used osteogenic disorder Shionogi mutant rats, which constitute an adequate model of the human redox regulation because both are unable to synthesize ascorbic acid. To study the long-term consequences of a glutathione deficit, we treated developing rats with L-buthionine-(S,R)-sulfoximine (BSO), an inhibitor of glutathione synthesis, and later investigated their behavior until adulthood. Moreover, some rats were treated with the dopamine uptake inhibitor GBR 12909 in order to elevate dopamine extracellular levels, thereby mimicking the dopamine hyperactivity proposed to be involved in schizophrenia. BSO and GBR 12909 alone or in combination minimally affected the development of spontaneous alternation or basic sensory and motor skills. A major effect of BSO alone or in combination with GBR 12909 was the induction of cataracts in both sexes, whereas GBR 12909 induced an elevation of body weight in females only. Sex and age-dependent effects of the treatments were observed in a test of object recognition. At postnatal day 65, whereas male rats treated with both BSO and GBR 12909 failed to discriminate between familiar and novel objects, females were not affected. At postnatal day 94, male object recognition capacity was diminished by BSO and GBR 12909 alone or in combination, whereas females were only affected by the combination of both drugs.Inhibition of brain glutathione synthesis and dopamine uptake in developing rats induce long-term cognitive deficits occurring in adulthood. Males are affected earlier and more intensively than females, at least concerning object recognition. The present study suggests that the low glutathione levels observed in schizophrenic patients may participate in the development of some of their cognitive deficits
PID Serval
serval:BIB_76952913CDAB
PMID
Date de création
2008-03-10T09:49:13.819Z
Date de création dans IRIS
2025-05-20T22:30:13Z