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Low brain glutathione and ascorbic acid associated with dopamine uptake inhibition during rat's development induce long-term cognitive deficit: relevance to schizophrenia.
Journal article

Low brain glutathione and ascorbic acid associated with dopamine uptake inhibition during rat's development induce long-term cognitive deficit: relevance to schizophrenia.

  • Castagné V Center for Research in Psychiatric Neuroscience, Department of Adult Psychiatry, Lausanne University-CHUV, CH-1008 Prilly, Lausanne, Switzerland. vincent.casagne@inst.hospvd.ch
  • Rougemont M
  • Cuenod M
  • Do KQ
  • 2004-01-31
Published in:
  • Neurobiology of disease. - 2004
Animals
Ascorbic Acid Deficiency
Body Weight
Brain
Brain Chemistry
Buthionine Sulfoximine
Cognition Disorders
Disease Models, Animal
Dopamine
Dopamine Plasma Membrane Transport Proteins
Dopamine Uptake Inhibitors
Enzyme Inhibitors
Female
Glutathione
Male
Maze Learning
Membrane Proteins
Nerve Tissue Proteins
Neurons
Oxidative Stress
Piperazines
Rats
Rats, Mutant Strains
Rats, Wistar
Recognition, Psychology
Schizophrenia
Synaptic Transmission
English Schizophrenia is associated with a cerebral glutathione deficit, which may leave the brain susceptible to oxidants. To study the 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 behaviour until adulthood. Since rodents may in some occasions compensate for a glutathione deficit by ascorbic acid (AA), we used Osteogenic Disorder Shionogi (ODS) mutant rats, which like humans, cannot synthetize ascorbic acid. Moreover, as hyperactivity of the dopaminergic system may be associated with schizophrenia, some rats were treated with the dopamine uptake inhibitor GBR 12909. Whereas ODS rats treated with either BSO or GBR 12909 alone had normal behaviour, rats treated with both BSO and GBR 12909 failed to discriminate between familiar and novel objects although other behaviours proved to be normal. In contrast, nonmutant rats were not affected by treatment with BSO and GBR 12909. Our results suggest that low brain glutathione and ascorbic acid levels associated with a perturbation of the dopaminergic system actively participate in the development of some cognitive deficits affecting schizophrenic patients.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/139235
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