The Complex Role of Serotonin–Dopamine–Glutamate Receptors in Major Depression

Major depressive disorder (MDD) is increasingly considered as a multifactorial neuropsychiatric disease involving dysregulation over multiple neurotransmitter systems. This chapter examines the complex role of serotonin, dopamine, and glutamate receptors in the pathophysiology of MDD, with a focus on their contributions to emotional regulation, reward processing, and synaptic plasticity. Recent evidence from pharmacological, genetic, and neuroimaging studies highlighted the involvement of receptor subtypes-such as 5-HT1A, 5-HT1A/C, D1-D3, and both ionotropic and metabotropic glutamate receptors-in mediating depressive symptoms and therapeutic responses. This chapter will point out potential targets for innovative and rapid-acting antidepressant strategies, emphasizing the need for personalized treatment approaches in MDD.