The effects of the lithium salt of GABA on the subcellular metabolic profile of L-arginine in the prefrontal cortex and striatum of rats during chronic stress

Abstract

Our previous data suggest that depression-like behavior of rats, which is induced by the 14-daylong unpredictable influence of stress factors, is accompanied by a sustained increase in the contents of L-arginine and nitric oxide (NO) and its stable metabolites, as well as stimulation of the inducible isoform of NO synthase (iNOS) and suppression of the activity of its constitutive NOS isoforms (cNOS) in the cytosol and mitochondria of the prefrontal cortex (PFC) and striatum. A single intraperitoneal injection of GABA lithium salt (at a dose of 0.9 mg/kg) on the second day of the post-stress period normalized the levels of L-arginine and active forms of nitrogen in cellular compartments from the PFC and striatum. Although this treatment did not influence the stress-induced shifts in the activity of cNOS, it prevented stimulation of the iNOS/NO system of mitochondria due to blockage of NO hyperproduction and nitrosative stress, whose development results in the disturbance of energetic processes in these brain areas.