Serine/threonine kinases as molecular targets of antidepressants: implications for pharmacological treatment and pathophysiology of affective disorders

It is currently a widely accepted opinion that adaptive. plastic changes in the molecular and cellular components of neuronal signaling systems correl ate with the effects on mood and cognition observed after long-term treatme nt with antidepressant drugs. Protein phosphorylation represents a key step for most signaling systems, and it is involved in the regulation of virtua lly all cellular functions. Two serine/threonine kinases. Ca2+/calmodulin-d ependent protein kinase II and cyclic AMP-dependent protein kinase. have be en shown to be activated in the brain following antidepressant treatment. T he changes in kinase activity are mirrored by changes in the phosphorylatio n of selected protein substrates in subcellular compartments (presynaptic t erminals and microtubules), which, in rum, ma), contribute to the modulatio n of synaptic transmission observed with antidepressants. The molecular con sequences of protein kinase activation may account for some of the alterati ons in neural function induced by antidepressants, and may suggest novel po ssible strategies of pharmacological intervention. (C) 2001 Elsevier Scienc e Inc. All rights reserved.