Introduction: Previous studies have shown that a single sub-anesthetic dose of ketamine exerts fast-acting antidepressant effects in patients and in animal models of depression. However, the underlying mechanisms are not totally understood. This study aims to investigate the effects of acute administration of different doses of ketamine on the immobility time of rats in the forced swimming test (FST) and to determine levels of hippocampal brain-derived neurotrophic factor (BDNF) and mammalian target of rapamycin (mTOR).
Methods: Forty male Wistar rats weighing 180-220 g were randomly divided into four groups (n = 10 each): group saline and groups ketamine 5, 10, and 15 mg/kg. On the first day, all animals were forced to swim for 15 min. On the second day ketamine (5, 10, and 15 mg/kg, respectively) was given intraperitoneally, at 30 min before the second episode of the forced swimming test. Immobility times of the rats during the forced swimming test were recorded. The animals were then decapitated. The hippocampus was harvested for determination of BDNF and mTOR levels.
Results: Compared with group saline, administration of ketamine at a dose of 5, 10, and 15 mg/kg decreased the duration of immobility (P < 0.05 for all doses). Ketamine at doses of both 10 and 15 mg/kg showed a significant increase in the expression of hippocampal BDNF (P < 0.05 for both doses). Ketamine given at doses of 5, 10, and 15 mg/kg showed significant increases in relative levels of hippocampal p-mTOR (P < 0.05 for all doses)
Conclusion: The antidepressant effect of ketamine might be related to the increased expression of BDNF and mTOR in the hippocampus of rats.