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In humans and in animal models, subanesthetic doses of ketamine, an N-methyl-D-aspartate antagonist, has induced rapid antidepressant effects, but few studies have examined its combination with classic antidepressant medications. Investigators explored this issue by using a model of depression induced in rats via unpredictable chronic mild stress.
In the 2-week trial, the rats were given ketamine, fluoxetine, imipramine, or saline alone or ketamine combined with either fluoxetine or imipramine. Stressed rats showed anhedonia (reduced preference for sucrose consumption), anxiety (limited exploration on an elevated open maze), and despair (learned helplessness; immobility during the forced-swimming test).
After 1 week, in the anhedonia and desp…