Neuronal proteins involved in synaptic targeting of AMPA receptors in rat hippocampus by antidepressant drugs.
Recent data suggest that the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptor subtype plays a pivotal role in the pathogenesis of effective disorders and in the action of antidepressant drugs. After chronic treatment with the antidepressants desipramine or paroxetine, we measured by immunoprecipitation and Western blotting, the changes in the interaction of AMPA receptor subunits with proteins involved in trafficking and/or stabilization of the subunits into synaptic membranes of the hippocampus. Both antidepressants increased the interaction of GluR1 subunit with stargazin and of GluR2/3 with NSF. Paroxetine increased the interaction of GluR1 with Rab4A, and desipramine markedly increased the interaction of GluR1 with SAP97. Paroxetine, but not desipramine, also increased membrane levels of CaMKII, autophosphorylated CaMKII and GluR1 phosphorylated at the CaMKII site. Interactions of GluR1 and GluR2/3 with proteins implicated in AMPA receptor trafficking and with scaffolding proteins appear to account for the enhanced membrane expression of AMPA receptors in the hippocampus after antidepressant treatment.
Martínez-Turrillas
Rebeca
R
Division of Neurosciences, CIMA, School of Medicine, University of Navarra, Av. Pio XII, 55, 31008 Pamplona, Spain.
Del Río
Joaquín
J
Frechilla
Diana
D
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D008297:Male; D009473:Neuronal Plasticity / Q000502:physiology*; D017374:Paroxetine / Q000494:pharmacology; D021122:Protein Subunits / Q000187:drug effects / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D018091:Receptors, AMPA / Q000187:drug effects* / Q000502:physiology; D013569:Synapses / Q000502:physiology*
D000928:Antidepressive Agents; D021122:Protein Subunits; D018091:Receptors, AMPA; D017374:Paroxetine; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D003891:Desipramine