The effect of prolonged imipramine and electroconvulsive shock treatment on calcium/calmodulin-dependent protein kinase II in the hippocampus of rat brain

The phosphorylation of substrate proteins by protein kinases plays a key ro le in signal transduction and function of neurons. Protein kinases have bee n associated with several physiological and pathological states including d epression. The aim of the present study was to investigate the effect of im ipramine and electroconvulsive treatment (ECS), both clinically effective t reatments of depression, on the activity of calcium/calmodulin dependent pr otein kinase II (CaM-KII) in the hippocampus. Our results indicate that rep eated (but not acute) imipramine and ECS administration significantly decre ased CaM-KII activity by 65 and 70%, respectively, in the soluble fractions from hippocampus. This decreased enzyme activity was accompanied by a prop ortional decrease (60-70%) of the amount of a-CaM-KII in the same fraction. A single and repeated administration of imipramine produced a significant increase in the activity of CaM-KII (50 and 337%, respectively) in the part iculate fraction from hippocampus. Similarly, a single and repeated ECS pro duced an increase in the enzyme activity by 22 and 240%, respectively. The amount of a-CaM-KII in the particulate fraction was not significantly affec ted by repeated antidepressant administration. It is postulated that change s in CaM-KII activity following chronic antidepressant treatment might repr esent and important step in expression of its antidepressive action. (C) 19 99 Elsevier Science Ltd. All rights reserved.