NEUROPHARMACOLOGY AND NEUROTOXICOLOGYAntidepressants activate CaMKII in neuron cell body by Thr286 phosphorylationTiraboschi, Ettore1; Giambelli, Roberto2; D'Urso, Giordano3; Galietta, Antonio3; Barbon, Alessandro4; de Bartolomeis, Andrea3; Gennarelli, Massimo2 4; Barlati, Sergio4; Racagni, Giorgio1 2; Popoli, Maurizio1 CAAuthor Information 1Center of Neuropharmacology-Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Via Balzaretti 9, 20133 Milano 2Genetics Unit, IRCCS Centro S. Giovanni di Dio-FBF, Brescia 3Department of Neuroscience and Behavioral Science, University Federico II, Naples 4Division of Biology and Genetics-Department of Biomedical Sciences and Biotechnology, University of Brescia, Italy CACorresponding Author: firstname.lastname@example.org Received 20 July 2004; accepted 19 August 2004 NeuroReport: October 25th, 2004 - Volume 15 - Issue 15 - p 2393-2396 Buy SDC Abstract CaM kinase II, a regulator of synaptic plasticity, is implicated in pathophysiology and pharmacology of psychiatric disorders. Chronic treatment with antidepressants desipramine and reboxetine up-regulated CaM kinase II in neuronal cell bodies of hippocampus. mRNA/protein expression for αCaM kinase II was unchanged, whereas Thr286 phosphorylation was increased in pyramidal/granular cell bodies, suggesting that increased phosphorylation is responsible for kinase activation. Short-term treatment of neuronal cultures with reboxetine reduced kinase activation in a concentration-dependent manner. The short-term inhibitory effect of reboxetine suggests that kinase up-regulation during antidepressant drug treatment is an adaptive response compensating for initial functional down-regulation. © 2004 Lippincott Williams & Wilkins, Inc.