Involvement of the NO synthase system in stress-mediated brain reactions.

The neurosis-like state developing as a result of chronic stress in animals and accompanied by transient cerebral hypoxia can lead to significant impairments to many brain structures. The effects of the humoral components of the stress reaction on the brain are mediated by both extra- and intracellular signal pathways, among which nitric oxide (NO) is of great importance. We report here immunohistochemical studies of the expression of the constitutive neuronal (nNOS) and inducible (iNOS) isoforms of NO synthase in neurons in the brains of white rats in conditions of chronic stress leading to the development of a neurosis- like state. Chronic stress was found to induce increases in nNOS and iNOS expression in many parts of the brain, predominantly in the neocortex and hippocampus. Administration of the nonspecific NOS inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (10 mg/kg) led to increases in the animals' depression, which was accompanied by reductions in motor and investigative activity assessed using traditional tests. This NOS inhibitor produced a minor increase in the expression of iNOS only. Thus, NO was shown to be involved in mediating the effects of stress with development of a neurosis-like state.