CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy.
Summary of "CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy."
RATIONALE:
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.
OBJECTIVES:
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.
Affiliation
Department of Psychiatry, Harvard Medical School-McLean Hospital, 115 Mill Street, MRC 215, Belmont, MA, 02478, USA, anita.bechtholt@gmail.com.
Journal Details
This article was published in the following journal.
Name: Psychopharmacology
ISSN: 1432-2072
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/21274700
- DOI: http://dx.doi.org/10.1007/s00213-011-2169-8
Medical and Biotech [MESH] Definitions
Phencyclidine
A hallucinogen formerly used as a veterinary anesthetic, and briefly as a general anesthetic for humans. Phencyclidine is similar to KETAMINE in structure and in many of its effects. Like ketamine, it can produce a dissociative state. It exerts its pharmacological action through inhibition of NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE). As a drug of abuse, it is known as PCP and Angel Dust.
Ketamine
A cyclohexanone derivative used for induction of anesthesia. Its mechanism of action is not well understood, but ketamine can block NMDA receptors (RECEPTORS, N-METHYL-D-ASPARTATE) and may interact with sigma receptors.
Maus Elberfeld Virus
A strain of ENCEPHALOMYOCARDITIS VIRUS, a species of CARDIOVIRUS, usually causing an inapparent intestinal infection in mice. A small number of mice may show signs of flaccid paralysis.
Balb 3t3 Cells
Cell lines developed from disaggregated BALB/c mouse embryos. They are extremely sensitive to CONTACT INHIBITION, and highly susceptible to transformation by SV40 VIRUS and murine sarcoma virus (SARCOMA VIRUSES, MURINE).
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