Prolonged effect of an anesthetic dose of ketamine on behavioral despair

The present study investigated the effect of a single, anesthetic dose of ketamine, a noncompetitive N-methyl-D-aspartate (NMDA) glutamate receptor antagonist, on behavioral despair, an animal model of depression. Separate groups of male Wistar rats injected with an anesthetic dose of ketamine (160 mg/kg ip) and tested 3, 7, or 10 days later showed significantly less immobility in the second of two forced-swim tests compared to saline-injected controls. Ketamine- and saline-treated animals did not differ significantly in the swim tests with respect to other behavioral measures, namely diving, jumping, and head shakes. The present findings point to an ameliorative effect of ketamine on behavioral despair and support the view that NMDA antagonists may have a beneficial effect on depression.