Ketamine inhibits long-term, but not intermediate-term memory formation in Lymnaea stagnalis

Abstract

We investigated the effects of the drug ketamine on procedural intermediate- and long-term memory formation in a well-established operant learning and memory model system, Lymnaea stagnalis. Animals were administered ketamine at discrete time points, ranging from 2 h pre-one-trial training (1TT) to 23 h post-1TT. Our results demonstrated that ketamine causes impairment of procedural memory formation, and that ketamine acts differentially, inhibiting only long-term memory (LTM) formation while having no effect on intermediate-term memory (ITM) formation. Ketamine's ability to inhibit LTM was found not to be due to state dependent learning implying that ketamine's effects are therefore specific to the molecular process involved in procedural LTM formation. Given past data from our laboratory, this suggests that ketamine may be exerting its differential effects by altering the gene transcription processes necessary and specific for LTM formation. Additionally, ketamine was found to have no effect on retrieval when administered 1 h before testing. However, ketamine was able to disrupt LTM formation when administered immediately before 1TT and up to 2 h after 1TT. Our findings suggest a longer period of consolidation after 1TT than previously demonstrated in Lymnaea, during which the procedural long-term memory remains labile and is vulnerable to disruption via amnestic agents, such as ketamine.