title: The emerging role of dopamine-glutamate interaction and of the postsynaptic density in bipolar disorder pathophysiology: Implications for treatment.
abstract: Aberrant synaptic plasticity, originating from abnormalities in dopamine and/or glutamate transduction pathways, may contribute to the complex clinical manifestations of bipolar disorder (BD). Dopamine and glutamate systems cross-talk at multiple levels, such as at the postsynaptic density (PSD). 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-glutamate 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. We also aim to discuss future therapeutic strategies that could selectively target the PSD-mediated signalling cascade at the crossroads of dopamine-glutamate neurotransmission.
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Section of Psychiatry, University Medical School of Naples "Federico II", Naples, Italy adebarto@unina.it.
authors.forename: Andrea
authors.initials: A
authors.lastname: de Bartolomeis
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Section of Psychiatry, University Medical School of Naples "Federico II", Naples, Italy.
authors.forename: Elisabetta F
authors.initials: EF
authors.lastname: Buonaguro
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Section of Psychiatry, University Medical School of Naples "Federico II", Naples, Italy.
authors.forename: Felice
authors.initials: F
authors.lastname: Iasevoli
authors.affiliation: Laboratory of Molecular and Translational Psychiatry, Department of Neuroscience, Section of Psychiatry, University Medical School of Naples "Federico II", Naples, Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Tomasetti
mesh_terms: D000339:Affect / Q000187:drug effects; D014150:Antipsychotic Agents / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D001921:Brain / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D004298:Dopamine / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D009473:Neuronal Plasticity; D057907:Post-Synaptic Density / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D014150:Antipsychotic Agents; D018698:Glutamic Acid; D004298:Dopamine
keywords: Akt; Antipsychotics; D2 receptor; Erk; GSK-3; Homer; NMDA receptor; PSD-95; mood stabilizers; synaptic plasticity