Nitric Oxide Signaling in Depression and Antidepressant Action

  • Gregers Wegener
  • Sâmia R. L. Joca


The pathogenesis of mood disorders remains elusive, but it is evident that multiple factors, genetic and environmental, play a crucial role for adult psychopathology and neurobiology. With regard to therapy, a significant proportion of affective disorder patients are partial or nonresponders, and there has been no major breakthrough in finding novel effective drug targets since the introduction of the current marketed antidepressant drugs in the 1950s to the 1980s, which all are based on monoaminergic pharmacological effects. Consequently, there exists a pressing need to develop novel treatment strategies – and ultimately understand the etiology and pathophysiology of affective disorders.

Nitric oxide serves an important role in the nervous system, where it acts as a messenger molecule in a number of physiological processes, including processes being linked to the major psychiatric diseases. This chapter will review general aspects of the NO system in major depressive disorder (MDD), as well as focus on the inhibition of NO production as putative therapeutic agents toward depression.


Methylene Blue NMDA Receptor Major Depressive Disorder Force Swim Test Taste Aversion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



GW was supported by the Danish Medical Research Council (Grant 11-107897) and the AU-IDEAS Initiative (eMOOD). SJ was supported by CNPq and FAPESP.

Conflicts of Interest

SJ declare no conflicts of interest. GW has received honorarium from H. Lundbeck A/S, AstraZeneca AB, Servier A/S, and Eli Lilly A/S.


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© Springer India 2016

Authors and Affiliations

  1. 1.Translational Neuropsychiatry Unit, Department of Clinical MedicineAarhus UniversityAarhusDenmark
  2. 2.Centre for Pharmaceutical Excellence, School of PharmacyNorth West UniversityPotchefstroomSouth Africa
  3. 3.Department of Physics and Chemistry, School of Pharmaceutical Sciences of Ribeirão PretoUniversity of São PauloSão PauloBrazil

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