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Aim. To study subcellular nitrergic response in the rat brain regions following chronic stress-induced depression-like behavior. Methods. An animal model of depression induced by chronic circadian stress (CCS) established in our laboratory was used. The L-arginine, L-citrulline and reactive nitrogen species (RNS) levels were determined spectrophotometrically. Results. Immediately after CCS and four days later, a depression-like behavior of rats was observed and accompanied by a substantial persistent elevation of the L-arginine, L-citrulline and RNS levels with a simultaneous up-regulation of the inducible nitric oxide synthase (iNOS) in both cytosolic and mitochondrial compartments of the rat prefrontal cortex, striatum, hippocampus, and hypothalamus, and a down-regulation of their cytosolic constitutive NOS isoforms (cNOS), mitochondrial cNOS was not significantly changed, with the exception for hypothalamus, in which the latter dropped. Conclusions. Compromised balance of the L-arginine levels and NO synthesis in both mitochondria and cytosol in the limbic brain appears to be implicated in the pathogenesis of depression and pathological anxiety

Institute of fine organic chemistry (FOC) of scientific technological center of organic and pharmaceutical chemistry NAS, Republic of Armenia EXPERIMENTAL Materials Depakine, containing sodium valproate (VPA) (Sanofi-Aventis U.S. LLC) as an active substance, d-amphetamine

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