The formation of a new gustatory memory trace in rats is prevented by the noncompetitive NMDA antagonist ketamine

Abstract

Blockade of the NMDA receptor with competitive or noncompetitive antagonists prevents the induction of long-term potentiation and blocks some forms of learning. These results and theoretical considerations provide support for a role of the NMDA receptor in memory formation. We investigated the role of the noncompetitive NMDA antagonist ketamine in taste-aversion learning in rats. One hour after exposing the animals for the first time to a saccharin solution (0.1%; CS), LiCl was injected to induce malaise (UCS). Forty-eight hours later, taste aversion was measured in a two-bottle choice test (saccharin vs. tap water). Ketamine (25 mg/kg) given 30 min before the first exposure to saccharin blocked taste-aversion learning. In contrast, animals injected with lower dosages (6 and 12 mg/kg), as well as saline-injected control animals, developed a strong avoidance of the sweet solution. Ketamine (25 mg/kg) given 10 min before the LiCl injection (drug administration between the CS and the UCS) did not block the association between the newly acquired gustatory trace and the malaise. The results from control groups showed that ketamine did not interfere with the retrieval of an already acquired taste aversion and that the results were not due to state-dependency effects. The NMDA receptor appears to play a role in the acquisition of a new taste cue but not in the association of a new taste cue with malaise. © 1990, Psychonomic Society, Inc.. All rights reserved.