title: Ketamine: synaptogenesis, immunomodulation and glycogen synthase kinase-3 as underlying mechanisms of its antidepressant properties.
abstract: Major depressive disorder is an extremely debilitating condition affecting millions of people worldwide. Nevertheless, currently available antidepressant medications still have important limitations, such as a low response rate and a time lag for treatment response that represent a significant problem when dealing with individuals who are vulnerable and prone to self-harm. Recent clinical trials have shown that the N-methyl-D-aspartate receptor antagonist, ketamine, can induce an antidepressant response within hours, which lasts up to 2 weeks, and is effective even in treatment-resistant patients. Nonetheless, its use is limited due to its psychotomimetic and addictive properties. Understanding the molecular pathways through which ketamine exerts its antidepressant effects would help in the developing of novel antidepressant agents that do not evoke the same negative side effects of this drug. This review focuses specifically on the effects of ketamine on three molecular mechanisms that are relevant to depression: synaptogenesis, immunomodulation and regulation of glycogen synthase kinase-3 activity.
authors.affiliation: Section of Stress, Psychiatry and Immunology, Department of Psychological Medicine, Institute of Psychiatry, King's College London, London, UK.
authors.forename: P A
authors.initials: PA
authors.lastname: Zunszain
authors.forename: M A
authors.initials: MA
authors.lastname: Horowitz
authors.forename: A
authors.initials: A
authors.lastname: Cattaneo
authors.forename: M M
authors.initials: MM
authors.lastname: Lupi
authors.forename: C M
authors.initials: CM
authors.lastname: Pariante
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D019208:Brain-Derived Neurotrophic Factor / Q000187:drug effects; D002940:Circadian Rhythm / Q000187:drug effects; D003865:Major Depressive Disorder / Q000188:drug therapy; D038362:Glycogen Synthase Kinase 3 / Q000187:drug effects*; D006801:Humans; D007155:Immunologic Factors / Q000494:pharmacology*; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use; D013569:Synapses / Q000187:drug effects*; D058570:TOR Serine-Threonine Kinases / Q000187:drug effects
chemical_list: D000928:Antidepressive Agents; D019208:Brain-Derived Neurotrophic Factor; D007155:Immunologic Factors; D007649:Ketamine; D058570:TOR Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3