FREE AND ZEOLITE-IMMOBILIZED PROBIOTIC MIXTURE VERSUS SODIUM VALPROATE IN PREVENTION OF OXIDATIVE STRESS AND MODULATION OF THE LARGININE INTRACELLULAR METABOLIC PATHWAYS IN THE RAT BRAIN AND BLOOD FOLLOWING DEXAMPHETAMINE- INDUCED BIPOLAR DISORDER
Experimental bipolar disorder (BD) was induced by repeated daily injection of the increasing doses of d-amphetamine sulfate (AMPH) (2-4 mg kg-1, 18 injections) in male young adult Wistar rats characterized by temporal arousal mimicked mania, and reduced exploratory and locomotor activities associated with behavioural depression under the condition of withdrawal of AMPH. At the end of the injection course, a stimulation of the lipid peroxidation processes and alterations in the mitochondrial and cytoplasmic activities of both arginase and nitric oxide synthase (NOS) were observed in the regions of brain corticolimbic system (prefrontal cortex, striatum, hippocampus and hypothalamus) and blood leukocytes. We have shown for the first time that a reversal treatment with the mixture of the specific probiotics with psycho- and antifungal activities in free (PMF) and zeolite-immobilized (PMZ) forms, and/or with a mood stabilizer, sodium valproate (VPA) inhibited oxidative stress and modulated differentially the L-arginine metabolic pathways in the brain and blood following AMPHinduced BD. Both PMF and PMZ efficiently normalized the activities of arginase isoforms and upregulated the suppressed intracellular NOS along with the gut microbiota restoration and prevention of the histopathological changes in the brain regions accompanied by normalization of rat behaviour.