Pathologic role of nitrergic neurotransmission in mood disorders.

Mood disorders are chronic, recurrent mental diseases that affect millions of individuals worldwide. Although over the past 40 years the biogenic amine models have provided meaningful links with the clinical phenomena of, and the pharmacological treatments currently employed in, mood disorders, there is still a need to examine the contribution of other systems to the neurobiology and treatment of mood disorders. This article reviews the current literature describing the potential role of nitric oxide (NO) signaling in the pathophysiology and thereby the treatment of mood disorders. The hypothesis has arisen from several observations including (i) altered NO levels in patients with mood disorders; (ii) antidepressant effects of NO signaling blockers in both clinical and pre-clinical studies; (iii) interaction between conventional antidepressants/mood stabilizers and NO signaling modulators in several biochemical and behavioral studies; (iv) biochemical and physiological evidence of interaction between monoaminergic (serotonin, noradrenaline, and dopamine) system and NO signaling; (v) interaction between neurotrophic factors and NO signaling in mood regulation and neuroprotection; and finally (vi) a crucial role for NO signaling in the inflammatory processes involved in pathophysiology of mood disorders. These accumulating lines of evidence have provided a new insight into novel approaches for the treatment of mood disorders.