Depression and the NMDA receptor/NO/cGMP pathway

Depression is a disorder, which has serious social and economic effects. It is evident that effective treatment helps restore quality of life, as about 50%–60% of patients with depression respond adequately to existing treatments based primarily on the monoaminergic system. However, the neurobiology of depression is not yet fully understood and several preclinical and clinical studies demonstrate the involvement of the glutamatergic system and the l-arginine/NO/cGMP pathway in the pathophysiology of depression. In fact, the N-methyl-d-aspartate receptor (NMDA) is a binding or modulating site for new and classic antidepressants, while various antidepressants also demonstrate altered nitric oxide levels in the body. Given this information, studies with NMDA receptor antagonist molecules and nitric oxide synthase enzyme inhibitors appear as effective possibilities for treating depression. Thus, this chapter will provide an overview of the involvement of NMDA receptors and the l-arginine/NO/cGMP pathway in depression, as well as the mechanisms, which contribute to the antidepressant response.