Original Investigation

Psychopharmacology

, Volume 215, Issue 4, pp 689-695

First online:

CD-1 and Balb/cJ mice do not show enduring antidepressant-like effects of ketamine in tests of acute antidepressant efficacy

  • Anita J. Bechtholt-GompfAffiliated withDepartment of Psychiatry, Harvard Medical School—McLean Hospital Email author 
  • , Karen L. SmithAffiliated withDepartment of Psychiatry, Harvard Medical School—McLean Hospital
  • , Catherine S. JohnAffiliated withDepartment of Psychiatry, Harvard Medical School—McLean Hospital
  • , Hannah H. KangAffiliated withDepartment of Psychiatry, Harvard Medical School—McLean Hospital
  • , William A. CarlezonJr.Affiliated withDepartment of Psychiatry, Harvard Medical School—McLean Hospital
  • , Bruce M. CohenAffiliated withDepartment of Psychiatry, Harvard Medical School—McLean Hospital
  • , Dost ÖngürAffiliated withDepartment of Psychiatry, Harvard Medical School—McLean Hospital

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Abstract

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.

Keywords

Ketamine Depression Antidepressant Animal models Balb/cJ CD-1 Mice