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 alphaCaM kinase II was unchanged, whereas Thr 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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Analysis of Variance
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Animals
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Antidepressive Agents / pharmacology*
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Blotting, Western / methods
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Calcium / metabolism
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases / genetics
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism*
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Cells, Cultured
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Desipramine / administration & dosage
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Enzyme Activation / drug effects
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Hippocampus / cytology*
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Immunohistochemistry / methods
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In Situ Hybridization / methods
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Male
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Morpholines / administration & dosage
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Neurons / drug effects*
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Neurons / metabolism
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Phosphorylation / drug effects
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RNA, Messenger / metabolism
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Rats
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Rats, Sprague-Dawley
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Reboxetine
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Threonine / metabolism*
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Time Factors
Substances
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Antidepressive Agents
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Morpholines
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RNA, Messenger
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Threonine
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Reboxetine
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Calcium-Calmodulin-Dependent Protein Kinase Type 2
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Calcium-Calmodulin-Dependent Protein Kinases
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Calcium
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Desipramine