cAMP-dependent binding proteins and endogenous phosphorylation after antidepressant treatment

Among the most significant changes induced in monoaminergic neurones by chronic antidepressant treatment are: reduction in tyrosine hydroxylase activity, decrease in the ability of NA to stimulate the activity of adenylate cyclase, and reduction in the concentration of noradrenergic and serotonergic receptors. Many synaptic and transsynaptic mechanisms may participate in the desensitization of neurotransmitter receptors after chronic treatment with antidepressants. The most commonly described effector mechanism beyond the second messengers depends on protein phosphorylation mediated by activation of specific protein serine-threonine kinases. Components of the protein phosphorylation system are associated with the cytoskeleton. This chapter investigates whether the cAMP-dependent phosphorylation system associated with microtubules, which are constituents of neuronal cytoskeleton, could be an intracellular target for antidepressants acting on NA and 5-HT neurones.