Ketamine Reduces Avoidance Responses During Re-Exposition to Aversive Stimulus: Comparison Between ()-Isomer and Racemic Mixture.

Background/objectives: Recent studies have investigated the effects of ketamine on fear memory in animals. However, it is unclear if ketamine might affect avoidance memory and emotional behaviors concomitantly. In this study, we compared the effects of (,)- and ()-ketamine in modulating avoidance responses, depression- and anxiety-related behaviors in stressed mice.

Methods: Mice were previously exposed to inescapable footshock stress, and 24 h later, they were trained in the active avoidance task. (,)-ketamine or ()-isomer was administered 1 h prior to re-exposition to the active avoidance task. Three hours after drug administration, mice were tested in the tail suspension, followed by the open field test.

Results: Neither form of ketamine affected avoidance memory retrieval, while ()-ketamine, and tangentially, (,) reduced avoidance responses during re-exposition to aversive stimulus. In the tail suspension test, (,)- and ()-ketamine equally evoked antidepressant effects. In the open field test, the racemic mixture, but not ()-ketamine, induced anxiolytic actions.

Conclusions: These findings reinforce the therapeutic potential of ketamine for the treatment of stress-related disorders, with (,)-ketamine being more effective in simultaneously inducing antidepressant and anxiolytic responses and reducing avoidance responses in stressed mice.