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2017 | 77 | Suppl.1 |
Tytuł artykułu

A relationship between glutathione deficiency during the early postnatal life and schizophrenia-like behavior in adulthood of sprague-dawley rats

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INTRODUCTION: A growing body of evidence implicates glutathione (GSH) deficiency and dysregulation of redox state in the pathophysiology of schizophrenia. AIM(S): The aim of the present study was to examine the effects of buthionine-S,R-sulfoximine (BSO)-mediated inhibition of glutamate cysteine ligase (GCL; an enzyme contributing to the GSH synthesis), during the early postnatal life on the GSH and cysteine (Cys) levels in the liver and kidney of 16-days old Sprague-Dawley rats and on the rat performance in the behavioral tests that were evaluated in the adulthood. METHOD(S): Male Sprague-Dawley pups between the postnatal day p5 and p16 were treated sc with the selective inhibitor of GCL, compound BSO (3.8 mmol/kg) and the dopamine reuptake inhibitor GBR 12909 (5 mg/kg every second day), alone or in combination. Biochemical parameters, i.e. GSH and cysteine (Cys) levels were determined in the rat liver and kidney 4h after the last doses of the drugs. Other groups of rats treated with BSO and GBR 12909 were examined during adulthood in the social interaction test (p42, p60, p90), novel object recognition test (p43, p61, p91) and in the open field test (p44, p63, p93). RESULTS: BSO alone or especially with GBR 12909 significantly decreased GSH level measured 4h after its last doses both in the liver and kidney. However, Cys concentration was distinctly reduced only in the kidney. Treatment with BSO and GBR 12909 induced deficits in both parameters of the social interaction test (number and time of interactions) assessed in the defined time points in adulthood. Such treatment also evoked a decrease in the memory retention in the novel object recognition test and an increase in exploratory activity in the open field test. CONCLUSIONS: Our results suggest that the inhibition of GSH synthesis and the dopamine reuptake during the early postnatal development induces in rats long-term behavioral changes that correspond to negative and positive symptoms of schizophrenia. FINANCIAL SUPPORT: Partially supported by statutory funds of the Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.
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  • Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
  • Jagiellonian University Medical College, Cracow,Poland
  • Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
  • Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland
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