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The PSD is a structural and functional protein mesh implicated in dopamine and glutamate-mediated synaptic plasticity. Proteins at PSD have been demonstrated to be involved in mood disorders pathophysiology and to be modulated by antipsychotics and mood stabilizers. On the other side, post-receptor effectors such as protein kinase B (Akt), glycogen synthase kinase-3 (GSK-3) and the extracellular signal-regulated kinase (Erk), which are implicated in both molecular abnormalities and treatment of BD, may interact with PSD proteins, and participate in the interplay of the dopamine\u2013glutamate signalling pathway. In this review, we describe emerging evidence on the molecular cross-talk between dopamine and glutamate signalling in BD pathophysiology and pharmacological treatment, mainly focusing on dysfunctions in PSD molecules. 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