Mood and behavior regulation: interaction of lithium and dopaminergic system.

Lithium is one of the most effect mood-stabilizing drugs prescribed especially for bipolar disorder. Lithium has wide range effects on different molecular factors and neural transmission including dopaminergic signaling. On the other hand, mesolimbic and mesocortical dopaminergic signaling is significantly involved in the pathophysiology of neuropsychiatric disorders. This review article aims to study lithium therapeutic mechanisms, dopaminergic signaling, and the interaction of lithium and dopamine. We concluded that acute and chronic lithium treatments often reduce dopamine synthesis and level in the brain. However, some studies have reported conflicting results following lithium treatment, especially chronic treatment. The dosage, duration, and type of lithium administration, and the brain region selected for measuring dopamine level were not significant differences in different chronic treatments used in previous studies. It was suggested that lithium has various mechanisms affecting dopaminergic signaling and mood, and that many molecular factors can be involved, including brain-derived neurotrophic factor (BDNF), cAMP response element-binding protein (CREB), ß-catenin, protein kinase B (Akt), and glycogen synthase kinase-3 beta (GSK-3ß). Thus, molecular effects of lithium can be the most important mechanisms of lithium that also alter neural transmissions including dopaminergic signaling in mesolimbic and mesocortical pathways.

Night shift hormone: How does melatonin affect depression?

Melatonin is the main hormone secreted by the pineal gland that modulates the circadian rhythm and mood. Previous studies have shown the therapeutic effects of melatonin, or its important analogue, agomelatine, on depression. In this review study, we aimed to discuss the potential mechanisms of melatonin involved in the treatment of depression. It was noted that disrupted circadian rhythm can lead to depressive state, and melatonin via regulating circadian rhythm shows a therapeutic effect. It was also noted that melatonin induces antidepressant effects via promoting antioxidant system and neurogenesis, and suppressing oxidative stress, neuroinflammation, and apoptosis. The interaction effect between melatonin or agomelatine and serotonergic signaling has a significant effect on depression. It was noted that the psychotropic effects of agomelatine are induced by the synergistic interaction between melatonin and 5-HT2C receptors. Agomelatine also interacts with glutamatergic signaling in brain regions involved in regulating mood and circadian rhythm. Interestingly, it was concluded that melatonin exerts both pro- and anti-inflammatory effects, depending on the grade of inflammation. It was suggested that synergistic interaction between melatonin and 5-HT2C receptors may be able to induce therapeutic effects on other psychiatric disorders. Furthermore, dualistic role of melatonin in regulating inflammation is an important point that can be examined at different levels of inflammation in animal models of depression.