Effects of agonists of NMDA and serotonin receptors at different stages of amnesia caused by impairment of long-term memory reconsolidation

Abstract

Previously we showed that in snails that were conditioned for food aversion impairment of memory reconsolidation MK-801, an antagonist of N-methyl-D-aspartate (NMDA) receptors, induced amnesia, at the early stage of which (<10 days) memory was restored after repeated conditioning. In contrast, at the late stages (≥10 days) repeated training did not lead to memory restoration. In the present study, we induced amnesia by MK-801/reminding in snails 24 h after taste aversion conditioning, and then tested the effects of an agonist of NMDA receptors and a serotonin precursor 5-hydroxytryptophan (5-HTP) at the early (day 3) and late (day 12) stages of amnesia. We found that NMDA injection and reminding by conditioned food stimulus 3 days after amnesia induction did not lead to memory restoration. However, repeated conditioning 15 days after the amnesia induction led to the restoration of memory. NMDA injection alone, not followed by reexposure, did not influence amnesia development. NMDA injection combined with reminding 12 days after the amnesia induction, as well as 5-HTP injection combined with a reminding 3 days after amnesia induction were ineffective, and a second conditioning did not result in the restoration of the memory. Thus, we have demonstrated that NMDA receptor agonists have an antiamnestic effect only during the early phase of amnesia development, which is caused by memory reconsolidation disruption, whereas the late phase of amnesia is insensitive to the agonists.