Lack of persistent effects of ketamine in rodent models of depression

Psychopharmacology (Berl). 2008 Jun;198(3):421-30. doi: 10.1007/s00213-008-1158-z. Epub 2008 May 7.


Rationale: We investigated the immediate and enduring effects of ketamine in behavioral and neurochemical assays predictive of antidepressant activity.

Materials and methods: One week after a single administration of ketamine (50-160 mg/kg), otherwise experimentally naive rats and mice were tested either in the forced swim test (FST) or the tail suspension test (TST). Other mice were also tested twice in the FST: immediately and 2 weeks after a single dose (1.25-50 mg/kg) of ketamine. In the next series of experiments, rats treated for 2 weeks twice daily with ketamine (50 or 160 mg/kg) or desipramine (10 mg/kg) were challenged with apomorphine and scored for locomotor activity and assayed for the density of cortical beta-adrenoceptors. The latter test was also carried out in rats that had received a single dose of ketamine (50 mg/kg) 1 week before the assay. The antidepressant-like (FST) and locomotor effects of ketamine (50 mg/kg) and desipramine (10 mg/kg) were assessed after their chronic (2 weeks, twice daily) administration as well.

Results: We report the lack of enduring antidepressant-like effect of ketamine in both rats and mice. A 2-week treatment with ketamine neither changed apomorphine-evoked locomotor hyperactivity nor did it decrease the density of cortical beta-adrenoceptors. However, some tolerance to the antidepressant-like effect of ketamine was noted in the FST, but it was accompanied by sensitization to its locomotor stimulatory effects.

Conclusions: These data indicate that ketamine neither produces enduring antidepressant-like effects in rodents nor does it display antidepressant-like behavioral or neurochemical effects after chronic treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents*
  • Antidepressive Agents, Tricyclic / pharmacology
  • Apomorphine / pharmacology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Depression / drug therapy*
  • Depression / psychology*
  • Desipramine / pharmacology
  • Dopamine Agonists / pharmacology
  • Drug Tolerance
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Exploratory Behavior / drug effects
  • Hindlimb Suspension / psychology
  • Ketamine / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Activity / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Rats, Wistar
  • Receptors, Adrenergic, beta / drug effects
  • Swimming / psychology


  • Antidepressive Agents
  • Antidepressive Agents, Tricyclic
  • Dopamine Agonists
  • Excitatory Amino Acid Antagonists
  • Receptors, Adrenergic, beta
  • Ketamine
  • Apomorphine
  • Desipramine