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Biol Psychiatry. 2016 May 1;79(9):776-786. doi: 10.1016/j.biopsych.2015.04.022. Epub 2015 May 4.

Ketamine as a Prophylactic Against Stress-Induced Depressive-like Behavior.

Author information

1
Departments of Neuroscience, Columbia University, New York.
2
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.
3
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.
4
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.
5
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.

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.

KEYWORDS:

Depression; Ketamine; Mice; PTSD; Stress; Stress resilience

PMID:
26037911
PMCID:
PMC4633406
DOI:
10.1016/j.biopsych.2015.04.022
[Indexed for MEDLINE]
Free PMC Article

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