Repeated Dosing of Ketamine in the Forced Swim Test: Are Multiple Shots Better Than One?
Frontiers in Psychiatry May 11, 2021 Ridge G. Weston, Paul J. Fitzgerald, Brendon O. Watson 19 citations
The anesthetic drug ketamine has been repurposed as a rapid-acting antidepressant for major depressive disorder (MDD), including treatment-resistant cases, unlike slower monoaminergic antidepressants. Its fast onset suggests a unique mechanism studied in reverse translational rodent models. Most research examines single ketamine doses, but MDD often requires ongoing treatment. This review of rodent studies using repeated ketamine dosing in the forced swim test (FST) found that repeated dosing can paradoxically increase immobility at high doses (50 or 100 mg/kg). However, several studies show repeated dosing more effectively decreases immobility than a single dose, with longer-lasting behavioral effects. The findings indicate repeated ketamine has prominent depression-related effects in rodents, which may help optimize human MDD treatment.