Abstract
Recent studies suggest that impaired glutathione synthesis and distorted dopaminergic transmission are important factors in the pathophysiology of schizophrenia. In the present study, on the postnatal days p5–p16, male pups were treated with the inhibitor of glutathione synthesis, L-buthionine-(S,R)- sulfoximine (BSO, 3.8 or 7.6 mmol/kg), and the dopamine uptake inhibitor, GBR 12,909 (5 mg/kg) alone or in combination, and prepulse inhibition of the acoustic startle response (PPI) was evaluated in adult 90-day-old rats. Moreover, the monoamine levels in the cortex and hippocampus of 16-day-old rats or 91-day-old rats were measured. The present results showed that administration of BSO at 3.8 mmol/kg led to a decreasing tendency in PPI for all tested prepulse intensities. In contrast, a combined treatment with BSO in both studied doses and GBR 12,909 did not induce significant deficits in PPI. Moreover, the results of biochemical studies indicated that treatment with BSO or GBR 12,909 alone induced a weak increase in the activity of dopaminergic, serotonergic, and noradrenergic systems in the frontal cortex and hippocampus of 16-day-old rats and 91-day-old rats. However, the combined administration of both substances allowed for maintaining the normal activity of monoaminergic systems in the rat brain. The most significant changes in the functioning of monoaminergic systems were observed in the frontal cortex of 16-day-old rats. Therefore, it seems that the frontal cortex of rat puppies is most sensitive to glutathione deficiencies resulting in increased oxidative stress in neurons. As a result, it can lead to cognitive and memory impairment.
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Abbreviations
- BSO :
-
L-butionine-(S,R)-sulfoximine
- DA :
-
Dopamine
- DOPAC :
-
3,4-Dihydroxyphenylacetic acid
- FCX :
-
Frontal cortex
- GBR 129,091 :
-
-[2-[Bis-4(fluorophenyl)methoxy]ethyl]-4–3-(3-phenylpropyl)piperazine hydrochloride
- 5-HIAA :
-
5-Hydroxyindoleacetic acid
- HPLC :
-
High-performance liquid chromatography
- 5-HT :
-
Serotonin
- HVA :
-
Homovanillic acid
- 2-MT :
-
3-Methoxytyramine
- NA :
-
Noradrenaline
- NM :
-
Normetanephrine
- ODS :
-
Osteogenic disorder Shionogi
- PPI :
-
Sensorimotor gating, prepulse inhibition test
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This study was financially supported by grant from the National Science Center 2016/23/B/NZ7/01280 and statutory funds of the Maj Institute of Pharmacology Polish Academy of Sciences, Cracow, Poland.
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Highlights
1. Multiple injections of BSO alone and in combination with GBR 12,909 do not disturb sensorimotor gating.
2. Treatment with GBR 12,909 causes an increase in dopamininergic and serotonergic system activity in the frontal cortex and hippocampus of rats on p 16 and p 91.
3. Treatment with BSO causes an increases in dopaminergic and noradrenergic system activity the frontal cortex and hippocampus of rats on p 91.
4. Combined administration of BSO and GBR 12,909 maintains the normal activity of the monoaminergic systems in the rat brain.
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Rogóż, Z., Lech, M.A., Chamera, K. et al. The Effect of Glutathione Deficit During Early Postnatal Brain Development on the Prepulse Inhibition and Monoamine Levels in Brain Structures of Adult Sprague–Dawley Rats. Neurotox Res 40, 733–750 (2022). https://doi.org/10.1007/s12640-022-00496-5
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DOI: https://doi.org/10.1007/s12640-022-00496-5