Plausible therapeutic effects of melatonin and analogs in the dopamine-associated pathophysiology of bipolar disorder

Bipolar disorder (BD) is a significant neuropsychiatric condition characterized by marked psychological mood disturbances. Despite extensive research on the symptomatology of BD, the mechanisms underlying its development and presentation remain unknown. Consequently, potential treatments are limited, and existing medications often cause significant side effects, leading to treatment discontinuation. Dopamine (DA) has been implicated in behavioral regulation, reward systems, and mood, highlighting the importance of the dopaminergic system in BD. Elevated levels of DA and tyrosine hydroxylase are associated with the onset of manic episodes, whereas reduced levels are linked to the depressive phase. Additionally, endogenous melatonin (MEL) levels are considerably lower in patients with BD. When administered as a treatment, exogenous MEL and MEL agonists improve behavioral characteristics and significantly modulate DA-related pathophysiological pathways in BD, with minimal adverse effects achieved through MEL receptor activation. Moreover, MEL and MEL agonists offer neuroprotection by promoting physiological homeostasis during disruption. The aim of this review is to investigate and propose MEL receptors as potential novel therapeutic targets for BD. This review seeks to analyze the role of MEL and its agonists in modulating dopamine-related pathophysiological pathways, improving behavioral outcomes, and providing neuroprotection with minimal side effects.