Modification of memory induced by lidocaine injection after learning in mice

Abstract

The present study was performed to investigate the effect of lidocaine on memory in mice using a novel multiple maze apparatus. After a 15 h fast, male ddY mice were placed in a multiple maze apparatus (water and food were placed at the entrance and exit of the maze, respectively) for 90 min (9: 00-10: 30a.m.) and allowed to learn the maze. Lidocaine (20-80mg/kg, i. p.) was injected either immediately after learning, 6 h after learning or 15 min before the trial, which was performed 24 h after learning. In the trial, the mouse was placed at the entrance, and the number of errors and the time (running time: RT) until the mouse reached the exit were counted. Administration of lidocaine immediately after learning influenced performance in the maze task: lidocaine 40mg/kg decreased both the number of errors and RT, whereas lidocaine 80mg/kg (convulsant dose) caused amnesia. In contrast, when lidocaine was injected 6 h after learning or 15 min before the trial, it had no effect on performance. A similar modification of memory was observed using picrotoxin, a GABA antagonist: i. e. picrotoxin 1mg/kg decreased both the number of errors and RT, whereas picrotoxin 4mg/kg (convulsant dose) caused amnesia. Pretreatment with diazepam 5mg/kg blocked both the memory-enhancing effect and memory-impairing effect of lidocaine. These findings suggest that lidocaine below the convulsant dose enhances memory consolidation through central nervous system excitation by blocking inhibitory synapses, and that lidocaine-induced convulsion impairs memory consolidation.