Ketamine Can Disrupt Episodic Memory (Hours to Days) Consolidation: Effects of Varying Dose and Retention Intervals

Memory consolidation is the process wherein short-term, episodic memories are converted into stable, long-term representations. Forebrain N-methy-d-aspartate receptors (NMDARs), particularly frontal cortical and hippocampal receptors, are thought to play a key role in neuronal plasticity and memory consolidation. Ketamine is an NMDA antagonist that disrupts memory, particularly encoding and retrieval processes. Previously we have observed no effect of post-acquisition ketamine treatment (50-100 mg/kg) on memory consolidation in rats performing a delayed-match-to place radial water maze task. The current study reexamined the effects of ketamine (25-100 mg/kg) on memory consolidation in this task over varying retention intervals (4, 24, and 48 hours). Consistent with previous data, no effect of ketamine treatment was seen at the four-hour retention interval. However, errors significantly increased at both the 24 and 48-hour intervals in rats treated with 100mg/kg ketamine. At 48 hours post-treatment, ketamine (25-100 mg/kg) produced a dose-dependent disruption of consolidation. These results indicate that a dose and delay dependent disruption of memory consolidation consequent of ketamine administration. In summary, these studies demonstrate that NMDA antagonism can disrupt consolidation of episodic memories.