Depression is one of the most common psychiatric illnesses. Patients often experience sadness, distrustfulness, low self-esteem and lose motivation to do activities they would have otherwise enjoyed. When these feelings become pervasive, persistent, and interfere with everyday activities it is called major depressive disorder (MDD). MDD is a complex condition that results from the disrupted interactions between genetic, physiological, psychological, and environmental factors. Its clinical manifestations include affective, cognitive, somatic and behavioral symptoms. Recent data from the National Comorbidity Survey Replication (NCS-R) indicates the lifetime prevalence of MDD at 16.6% and the 1-year prevalence at 6.7%.
Currently prescribed drugs to treat or manage MDD include monoamine oxidase (MAO) inhibitors, and 5-HT and norepinephrine (NE) reuptake inhibitors. Other antidepressants, such as fluoxetine, are widely prescribed. However, their mechanisms of action are not known. Neurotrophic factors such as brain-derived neurotrophic factor (BDNF), can contribute to the therapeutic effects of antidepressant treatments as well. Recently, modulation of the glutamatergic system has become an attractive strategy for discovering new-generation antidepressants. Some studies have revealed that α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors activation were required for eliciting the antidepressant-like effects in both acute and chronic stress models of depression .