L-NAME, a Non Selective Nitric Oxide Synthase, Affects Stress-Related Behaviors and Glial Cell-Derived Neurotrophic Factor Expression in Restrained Adolescent ICR Mice / 대한정신약물학회지

ABSTRACT

OBJECTIVE: Depending on genetic or environmental effects over adolescent development, typical behavioral responses come out in adolescence. Also, alteration of nitric oxide (NO) levels in the brain has been associated with modifications of stress related behavior. Present study was designed to investigate the possible influence of chronic stress from restraint on the generation of depression in adolescent mice, and also to evaluate whether NO has modulatory roles in the behavioral and biological reactions. METHODS: ICR mice exposed to stressful restraint, 2 h per day, was treated with NG-nitro L-arginine methyl ester (L-NAME) (10 mg/kg), a non-selective NO synthase (NOS) inhibitor. To evaluate depression-like behavior in the mice, forced swim test and open field test were performed after the last restraint. To investigate stress-induced changes in the expression level of glial cell-derived neurotrophic factor (GDNF), free-floating immunohistochemistry was performed. RESULTS: The results showed that stressed group has longer immobility time and less crossing number in forced swimming and open field test, and that these stress responses were significantly prevented by L-NAME. Furthermore, decreased GDNF expression in the hippocampus by stress was prevented to that of controls within the L-NAME treated group. CONCLUSION: The results suggest that stress and NO signaling could be involved in generation of depression in adolescence. It also suggested that GDNF might contribute to prevent stress-related behaviors.