title: Ketamine as a Prophylactic Against Stress-Induced Depressive-like Behavior.
abstract: BACKGROUND
  Stress exposure is one of the greatest risk factors for psychiatric illnesses like major depressive disorder and posttraumatic stress disorder. However, not all individuals exposed to stress develop affective disorders. Stress resilience, the ability to experience stress without developing persistent psychopathology, varies from individual to individual. Enhancing stress resilience in at-risk populations could potentially protect against stress-induced psychiatric disorders. Despite this fact, no resilience-enhancing pharmaceuticals have been identified.
  
  
  METHODS
  Using a chronic social defeat (SD) stress model, learned helplessness (LH), and a chronic corticosterone (CORT) model in mice, we tested if ketamine could protect against depressive-like behavior. Mice were administered a single dose of saline or ketamine and then 1 week later were subjected to 2 weeks of SD, LH training, or 3 weeks of CORT.
  
  
  RESULTS
  SD robustly and reliably induced depressive-like behavior in control mice. Mice treated with prophylactic ketamine were protected against the deleterious effects of SD in the forced swim test and in the dominant interaction test. We confirmed these effects in LH and the CORT model. In the LH model, latency to escape was increased following training, and this effect was prevented by ketamine. In the CORT model, a single dose of ketamine blocked stress-induced behavior in the forced swim test, novelty suppressed feeding paradigm, and the sucrose splash test.
  
  
  CONCLUSIONS
  These data show that ketamine can induce persistent stress resilience and, therefore, may be useful in protecting against stress-induced disorders.
authors.affiliation: Departments of Neuroscience, Columbia University, New York.
authors.forename: Rebecca A
authors.initials: RA
authors.lastname: Brachman
authors.affiliation: Departments of Psychiatry, Columbia University, New York.; Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.
authors.forename: Josephine C
authors.initials: JC
authors.lastname: McGowan
authors.affiliation: Departments of Psychiatry, Columbia University, New York.; Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.
authors.forename: Jennifer N
authors.initials: JN
authors.lastname: Perusini
authors.affiliation: Departments of Psychiatry, Columbia University, New York.; Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.
authors.forename: Sean C
authors.initials: SC
authors.lastname: Lim
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR-S 1178 Santé Publique, Santé Mentale, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, France.
authors.forename: Thu Ha
authors.initials: TH
authors.lastname: Pham
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR-S 1178 Santé Publique, Santé Mentale, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, France.
authors.forename: Charlene
authors.initials: C
authors.lastname: Faye
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR-S 1178 Santé Publique, Santé Mentale, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, France.
authors.forename: Alain M
authors.initials: AM
authors.lastname: Gardier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR-S 1178 Santé Publique, Santé Mentale, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, France.
authors.forename: Indira
authors.initials: I
authors.lastname: Mendez-David
authors.affiliation: Institut National de la Santé et de la Recherche Médicale UMR-S 1178 Santé Publique, Santé Mentale, Université Paris-Sud, Fac Pharmacie, Université Paris Saclay, France.
authors.forename: Denis J
authors.initials: DJ
authors.lastname: David
authors.affiliation: Departments of Psychiatry, Columbia University, New York.; Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.; Department of Pharmacology, Columbia University, New York, New York.
authors.forename: René
authors.initials: R
authors.lastname: Hen
authors.affiliation: Departments of Psychiatry, Columbia University, New York.; Division of Integrative Neuroscience, New York State Psychiatric Institute/Research Foundation for Mental Hygiene, Inc., New York, New York.. Electronic address: cad2125@cumc.columbia.edu.
authors.forename: Christine A
authors.initials: CA
authors.lastname: Denny
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage*; D001007:Anxiety; D003345:Corticosterone / Q000008:administration & dosage; D003863:Depression / Q000209:etiology / Q000517:prevention & control*; D005239:Fear / Q000187:drug effects; D006380:Helplessness, Learned; D007649:Ketamine / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055500:Resilience, Psychological / Q000187:drug effects*; D012919:Social Behavior; D013315:Stress, Psychological / Q000150:complications*
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine; D003345:Corticosterone
keywords: Depression; Ketamine; Mice; PTSD; Stress; Stress resilience