title: Antidepressant drug action--From rapid changes on network function to network rewiring.
abstract: There has been significant recent progress in understanding the neurobiological mechanisms of antidepressant treatments. The delayed-onset of action of monoamine-based antidepressant drugs have been associated to their ability to slowly increase synaptic plasticity and neuronal excitability via altering neurotrophic signaling (synthesis of BDNF and activation of its receptor TrkB), dematuration of GABAergic interneurons and inhibition of "breaks of plasticity". On the other hand, antidepressants rapidly regulate emotional processing that - with the help of heightened plasticity and appropriate rehabilitation - gradually lead to significant changes on functional neuronal connectivity and clinical recovery. Moreover, the discovery of rapid-acting antidepressants, most notably ketamine, has inspired interest for novel antidepressant developments with better efficacy and faster onset of action. Therapeutic effects of rapid-acting antidepressants have been linked with their ability to rapidly regulate neuronal excitability and thereby increase synaptic translation and release of BDNF, activation of the TrkB-mTOR-p70S6k signaling pathway and increased synaptogenesis within the prefrontal cortex. Thus, alterations in TrkB signaling, synaptic plasticity and neuronal excitability are shared neurobiological phenomena implicated in antidepressant responses produced by both gradually and rapid acting antidepressants. However, regardless of antidepressant, their therapeutic effects are not permanent which suggests that their effects on neuronal connectivity and network function remain unstable and vulnerable for psychosocial challenges.
authors.affiliation: Neuroscience Center, P.O. Box 56, FI-00014, University of Helsinki, Helsinki, Finland. Electronic address: tomi.rantamaki@helsinki.fi.
authors.forename: Tomi
authors.initials: T
authors.lastname: Rantamäki
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, Centre National de la Recherche Scientifique, FR-67084 Strasbourg Cedex, France.
authors.forename: Ipek
authors.initials: I
authors.lastname: Yalcin
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D003866:Depressive Disorder / Q000188:drug therapy* / Q000503:physiopathology*; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology*; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents
keywords: Antidepressant; Emotional processing; Neurotrophin; Synaptic plasticity; Synaptogenesis