Neuroplasticity and Mechanisms of Action of Acute and Chronic Treatment with Antidepressants at an Experimental Level

The neurobiology of depression establishes a close relationship between this psychiatric disorder and alterations in neuroplasticity associated with neuronal atrophy and a reduction in dendritic arborization in the prefrontal cortex and hippocampus. In this sense, the therapeutic effect of antidepressants is associated with changes in the brain associated with neuroplasticity, neurogenesis and synaptogenesis through the activation of intracellular signaling pathways associated with changes at the neurochemical and behavioral level in animal models used to study depression. Antidepressants increase the synaptic availability of monoamines (monoaminergic hypothesis) such as serotonin, noradrenaline and GABA by inhibiting their reuptake or degradation and activating intracellular signaling pathways such as the cAMP-CREB cascade, which regulates the expression of genes related to neuroplasticity and neurogenesis in various brain structures associated with depression. Although acute treatment alters the number of receptors, the therapeutic effect lasts 3-4 weeks and depends on the increase in the density of dendritic spines and the expression of proteins such as BDNF and GAP-43 in the hippocampus and cerebral cortex. This review focuses on the effects of acute and chronic treatment with monoaminergic antidepressants and new drugs and other pharmacological alternatives in preclinical studies with the aim of demonstrating their mechanism of action and relationship to neuroplasticity.