Investigation of the Role of L-Arginine and L-NAME in Dorsal Hippocampus on Anxiety, Depression and Brain Level of BDNF after Stress in Male Mice

Nitric oxide is involved in response to stress-induced anxiety and depression in the dorsal hippocampus. In this study we investigated the effects of L-arginine and L-NAME in the dorsal hippocampus on anxiety, depression, and brain-derived neurotrophic factor (BDNF) levels in stressed male NMRI mice.

Electric foot-shock stress (10 Hz, 40 mV for 60 seconds) was applied to animals for four consecutive days. Three doses of L-arginine or L-NAME (1, 5 and 10 μg/mouse) were injected bilaterally into the dorsal hippocampus five minutes before starting foot-shock stress. Anxiety and depression-like behaviors and brain BDNF levels were measured 24 hours after stress using an elevated plus maze, forced swim test, and ELISA, respectively.

Injection of different doses of L-arginine and L-NAME before stress showed that the number of entries in the open arm decreased in elevated plus maze. The number of entries in the closed arm increased more in the stress group than that in the control group. Also, intra dorsal hippocampus injections of different doses of L-arginine and L-NAME before stress significantly decreased swimming time and increased floating and struggling time in the forced swim test compared to the control group. In addition, ELISA results showed that injections of different doses of L-arginine and L-NAME before stress had no significant effects on brain BDNF level.

Nitric oxide in the dorsal hippocampus may mediate the induced anxiety and depression behaviors by foot-shock stress.