Genetic and environmental influences on one-trial conditioned context aversion in mice

İlhan, Çınar Furkan; Urcelay, Gonzalo P.; Kışlal, Sezen

Abstract

Anticipatory nausea (AN) is caused by an association between contextual cues and the experience of nausea (the side effects of chemotherapy or radiation treatment) and it develops predominantly in female patients undergoing chemotherapy. Preclinical studies in rodents show that the administration of an illness‐inducing agent in the presence of novel contextual cues can cause conditioned context aversion (CCA) and this has been proposed to model AN. The literature also suggests that brief pre‐exposure to a novel context prior to shock delivery is critical in the development of contextual fear conditioning in rodents (a phenomenon known as Immediate Shock Deficit), but this has not been assessed in CCA. The aim of present study was to develop a CCA paradigm to assess this in outbred (CD1) and inbred (C57BL/6J) mice and evaluate potential sex differences. The results revealed that a single conditioning trial in which a distinctive context was paired with LiCl‐induced illness was sufficient to elicit a conditioned response in both female and male CD1 outbred mice, but not in C57BL/6J inbred mice. In addition, CCA was facilitated when animals had prior experience with the context. Finally, outbred female mice showed longer and more robust retention of CCA than male mice, which parallels clinical findings. The results indicate the importance of using CD1 outbred mice as an animal model of AN as well as examining sex differences in the CCA paradigm. Similar findings in humans encourage the future use of this novel CCA preclinical mouse model.

Citation

İlhan, Ç. F., Urcelay, G. P., & Kışlal, S. (2023). Genetic and environmental influences on one-trial conditioned context aversion in mice. Genes, Brain and Behavior, Article e12857. https://doi.org/10.1111/gbb.12857

• Journal Article Type: Article
• Acceptance Date: Jun 17, 2023
• Online Publication Date: Jun 26, 2023
• Publication Date: Jun 26, 2023
• Deposit Date: Jul 17, 2023
• Publicly Available Date: Jul 24, 2023
• Journal: Genes, Brain and Behavior
• Print ISSN: 1601-1848
• Electronic ISSN: 1601-183X
• Publisher: Wiley
• Peer Reviewed: Peer Reviewed
• Article Number: e12857
• DOI: https://doi.org/10.1111/gbb.12857
• Keywords: contextual learning, anticipatory nausea, one‐trial conditioning, chemotherapy, strain differences, pre‐exposure, mice, sex differences, cancer, conditioned context aversion
• Public URL: https://nottingham-repository.worktribe.com/output/22449912
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1111/gbb.12857
• Additional Information: Received: 2023-04-03; Accepted: 2023-06-17; Published: 2023-06-26