Ketamine facilitates appetitive trace conditioning in mice: Further evidence for abnormal stimulus representation in schizophrenia model animals.

Abstract

Recent studies indicated that positive symptoms of schizophrenia, such as hallucination and delusion, can be modeled using Pavlovian conditioning procedures. Various schizophrenia model animals exhibit abnormally strong associative activations of absent stimuli (i.e., conditioned hallucination) and readily form further associations involving the absent cues (i.e., enhanced mediated conditioning). In the present study using mice, we examined whether the acquisition of appetitive trace conditioning, another Pavlovian task in which animals must form associations between two stimuli that never occur together, is facilitated by injections of ketamine, an N-methyl-D-aspartate-receptor antagonist and a known hallucinogen at low doses in humans and nonhuman animals. Ketamine administration before each conditioning session significantly enhanced the acquisition of 4-s trace conditioning but not delay conditioning. The trace conditioning-specific facilitatory effect of ketamine was replicated in subsequent experiments in which slightly modified procedures were used to enhance the overall levels of conditioned responses. Taken together, the current results demonstrated that low-dose ketamine promotes associative learning between stimuli over a temporal gap, which adds to existing literature illustrating aberrant learning involving absent stimuli in schizophrenia model animals. We discuss potential associative mechanisms through which ketamine promoted trace conditioning with reference to Wagner's (1981) Standard Operating Procedures model. (PsycInfo Database Record (c) 2023 APA, all rights reserved).