title: CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy.
abstract: BACKGROUND
  In patients, ketamine is a fast-acting antidepressant that can induce long-lasting symptom relief. Similar rapid effects have been reported in rodents, but reports of lasting effects are limited.
  
  
  OBJECTIVE
  We sought to extend past findings by examining dose-response curves that overlap with the individual doses previously reported to induce lasting effects in rodents and determining whether effects generalize to the tail suspension test (TST) and Balb/cJ mice.
  
  
  METHODS
  Using common tests of antidepressant efficacy we first confirmed our ability to detect the effects of desipramine, a well-characterized antidepressant drug. Next, we sought to determine whether two non-competitive NMDA antagonists, ketamine and MK-801, had long-lasting antidepressant-like effects in CD-1 mice, a strain that has often been used to demonstrate the short-term antidepressant-like effects of ketamine. Finally, we examined the short- and long-term effects of ketamine in a mouse strain that is more sensitive to antidepressant-like effects, Balb/cJ mice.
  
  
  RESULTS
  In CD-1 mice, desipramine treatment yielded significant short-term antidepressant-like effects in the TST and the forced swimming test (FST). However, no significant enduring effects of ketamine or MK-801 were observed 1 week later. Short-term effects of ketamine in the TST were observed in Balb/cJ mice, but lasting effects were absent 1 week later.
  
  
  CONCLUSIONS
  Although the TST and FST have been widely used to detect antidepressant-like effects in mice, they do not appear to be sensitive to long-lasting antidepressant-like effects of ketamine in mice and, therefore, do not model the therapeutic effects of ketamine that have been reported in humans with major depression.
authors.affiliation: Department of Psychiatry, Harvard Medical School-McLean Hospital, 115 Mill Street, MRC 215, Belmont, MA 02478, USA. anita.bechtholt@gmail.com
authors.forename: Anita J
authors.initials: AJ
authors.lastname: Bechtholt-Gompf
authors.forename: Karen L
authors.initials: KL
authors.lastname: Smith
authors.forename: Catherine S
authors.initials: CS
authors.lastname: John
authors.forename: Hannah H
authors.initials: HH
authors.lastname: Kang
authors.forename: William A
authors.initials: WA
authors.lastname: Carlezon
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Cohen
authors.forename: Dost
authors.initials: D
authors.lastname: Ongür
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D019417:Hindlimb Suspension; D007649:Ketamine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D013045:Species Specificity; D013550:Swimming; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D007649:Ketamine