Ketamine differentially affects implicit and explicit memory processes in rats

Ketamine, a non-competitive NMDA receptor antagonist, produces antidepressant effects at subanesthetic doses. The therapeutic effect, however, is often accompanied by cognitive side effects, including memory impairments. Yet, the specific effects of ketamine on different processes of implicit and explicit memory remain to be elucidated.

We examined the effect of an antidepressant dose of ketamine (10 mg/kg, IP) on the encoding, retrieval, and modulation processes of fear memory and spatial memory in adult Wistar rats.

Ketamine was administered before the fear acquisition, retrieval, or extinction procedures in a Pavlovian fear conditioning task. In another set of experiments, it was administered before the training, probe trial, or reversal training phases of the Morris Water Maze (MWM).

The antidepressant dose of ketamine partially impaired fear extinction when administered before the acquisition or retrieval. In contrast, it facilitated memory modulation and decreased the escape latency in the first day of reversal training in the MWM when administered before the training or reversal training sessions. Encoding or retrieval performance in either type of memory was not affected.

These findings show that ketamine does not impair the acquisition or retrieval processes of cued fear or spatial memory; but exerts differential effects on memory modulation of these implicit and explicit memory paradigms, by disrupting fear extinction and facilitating reversal spatial learning.