title: Cellular and molecular mechanisms in the long-term action of antidepressants.
abstract: The hypotheses on the pathophysiology of depression/mood disorders and on antidepressant mechanisms have greatly changed in recent years. The classical monoamine hypothesis was revealed to be simplistic, in that it could not explain the temporal delay in the therapeutic action of antidepressants. Converging lines of evidence have shown that adaptive changes in the several mechanisms of neuroplasticity are likely to be the cellular and molecular correlates of therapeutic effect. In this article, several mechanisms of neuroplasticity are analyzed in relation to the mechanism of antidepressants, ranging from changes in gene expression (including neurotrophic mechanisms), to synaptic transmission and plasticity, and neurogenesis. We propose that the current version of the hypothesis of antidepressant mechanism simply be called the "hypothesis of neuroplasticity". In the final section, we also briefly review the main current novel strategies in the pharmacology of depression and the new putative targets for antidepressants, with particular emphasis on nonmonoaminergic mechanisms.
authors.affiliation: Center of Neuropharmacology, Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milano, Italy.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Racagni
authors.forename: Maurizio
authors.initials: M
authors.lastname: Popoli
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D015306:Biogenic Monoamines / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000502:physiology; D049109:Cell Proliferation; D003866:Depressive Disorder / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D000928:Antidepressive Agents; D015306:Biogenic Monoamines; D019208:Brain-Derived Neurotrophic Factor