Effect of Nitric Oxide on Basolateral Amygdala on Persistence of Anxiety and Depression in Stressed Male Rats

Introduction: The current study aimed at investigating the role of Nitric Oxide (NO) in the maintenance of anxiety and depression induced by stress in male Wistar rats using intra-Basolateral Amygdala (BLA) injection of NO precursor, L-arginine, Nitric Oxide Synthase (NOS) inhibitor, and L-NAME.  Methods: Two 23-gauge stainless steel cannulas were placed in the BLA, stereotaxically. Seven days later, animals experienced electro foot shock stress based on the following protocol: animals experienced four sessions of stress for 60 minutes in four consecutive days. Five minutes before each stress session, the animals received different doses of L-arginine or L-NAME (1, 5 and, 10 μg/rat) or saline (0.5 μL/rat) intra-BLA. Six days after the stress termination, animals were tested for maintenance of anxiety-like behavior (elevated plus maze; EPM) and eight days after the stress they were examined for depression (forced swimming test; FST). Results: Stress reduced the time and number of open arms and decreased motor activity on EPM. Stress-induced anxiety was inhibited by L-arginine and L-NAME (1, 5, and 10 µg/rat). L-Arginine and L-NAME induced anxiety in non-stressed rats. Stress also increased the immobility time in animals in FST paradigm. Interestingly, both L-arginine and L-NAME, in all doses reduced the stress effect. Conclusion: BLA nitric oxide may play a pivotal role in anxiety and depression induced by stress in rats. Since the effects of both L-arginine and L-NAME were similar, NO might have a modulatory role in the BLA.