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Ketamine Facilitates Appetitive Trace Conditioning in Mice: Further Evidence for Abnormal Stimulus Representation in Schizophrenia Model Animals

Ketamine Facilitates Appetitive Trace Conditioning in Mice: Further Evidence for Abnormal... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Behavioral Neuroscience American Psychological Association

Ketamine Facilitates Appetitive Trace Conditioning in Mice: Further Evidence for Abnormal Stimulus Representation in Schizophrenia Model Animals

Suzuki, Riria; Kosaki, Yutaka
Behavioral Neuroscience , Volume 137 (4): 18 – Aug 1, 2023
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Publisher
American Psychological Association
Copyright
© 2023 American Psychological Association
ISSN
0735-7044
eISSN
1939-0084
DOI
10.1037/bne0000559
Publisher site
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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.

Journal

Behavioral Neuroscience – American Psychological Association

Published: Aug 1, 2023

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