title: Antidepressants encounter autophagy in neural cells.
abstract: The prevailing view of antidepressants' (ADs) mode of action primarily focuses on their impact on neurotransmitter circuits, since the corresponding transporters and receptors are common targets of ADs. However, mounting evidence points to additional target structures, which may either support the beneficial effects or account for undesired side effects of ADs. Recently, we analyzed the influence of three ADs of different classes on autophagy-related processes in primary astrocytes and neurons. While amitriptyline (AMI) and citalopram (CIT) upregulate the expression of autophagic markers such as LC3B-II or Beclin 1, venlafaxine fails to exert these effects. Autophagy triggered by AMI and CIT is functional in terms of autophagic flux, and is partially mediated by class III PtdIns 3-kinase- and ROS dependent-pathways. Together, our study's results highlight a novel mode of action of ADs beyond monoaminergic neurotransmission.
authors.affiliation: Max Planck Institute of Psychiatry, Chaperone Research Group, Munich, Germany. zschocke@mpipsykl.mpg.de
authors.forename: Jürgen
authors.initials: J
authors.lastname: Zschocke
authors.forename: Theo
authors.initials: T
authors.lastname: Rein
mesh_terms: D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D017209:Apoptosis; D001253:Astrocytes / Q000378:metabolism; D001343:Autophagy; D001921:Brain / Q000378:metabolism; D015283:Citalopram / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D009154:Mutation; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D017510:Protein Folding; D017382:Reactive Oxygen Species
chemical_list: D000928:Antidepressive Agents; D018377:Neurotransmitter Agents; D017382:Reactive Oxygen Species; D015283:Citalopram; D000639:Amitriptyline; D019869:Phosphatidylinositol 3-Kinases