Kamin blocking is disrupted by low-dose ketamine in mice: Further implications for aberrant stimulus processing in schizophrenia.

Abstract

Previous studies have shown that low doses of ketamine, an N-methyl-D-aspartate receptor antagonist, produce aberrantly strong internal representations of associatively activated but absent stimuli in humans and nonhuman animals, suggesting the validity of ketamine treatment as a preclinical model of the positive symptoms of schizophrenia, including hallucinations and delusions. However, whether acute ketamine treatment also impairs the ability to ignore present but informationally redundant stimuli, which is another hallmark of schizophrenia, remains unclear. Accordingly, the present study investigated whether injections of low-dose ketamine attenuate Kamin blocking in an appetitive conditioning preparation in mice. Mice in the blocking group were initially trained with A+ conditioning (i.e., conditioned stimulus A paired with a sucrose solution), followed by compound AX+ training, before the conditioned responses to the cue X were tested in extinction. The animals in the control group received B+ training before the AX+ training. Half of the mice in each group received an injection of 16 mg/kg ketamine before each compound conditioning session and the extinction test, whereas the other half received saline. The results showed a reliable blocking effect in the saline-treated mice, whereas the blocking effect was absent in the ketamine-treated mice. Specifically, the absence of blocking was due to the ketamine-treated mice learning about the blocked cues. This finding further validates the use of low-dose ketamine as a preclinical model of schizophrenia. It also suggests a possible link between hallucination-like aberrant processing of absent events and a reduced ability to suppress attentional processing of task-irrelevant stimuli. (PsycInfo Database Record (c) 2024 APA, all rights reserved).