Treatment of cisplatin-induced olfactory aversion based on selection logic: A novel approach

Aversion can arise from a combination of unconditioned stimuli that induce physical discomfort, such as pain and nausea. Chemotherapy-induced side effects, including taste and olfactory aversion, can persist even after treatment has ended, thereby reducing the quality of life. Currently, however, no effective pharmacological interventions exist for treating chemotherapy-induced conditioned aversion learning. Therefore, elucidating its underlying mechanisms is of great importance. In this study, we investigated cisplatin-induced olfactory aversion learning using the two-bottle choice test. Cisplatin was found to induce aversive responses to neutral odorants, namely isoamyl acetate and benzaldehyde. Notably, we obtained two key findings. First, an odor solution that was not aversive in the two-bottle choice test (i.e., distilled water) became aversive to mice when compared with a third novel odor solution that had not been presented in the test. Second, when pairs of three odorants were alternated over an extended period, the mice occasionally shifted their aversive responses as the pairings changed. In clinical practice, patients are exposed to a variety of odors. Thus, the new insights gained from this study on olfactory aversion may help inform the development of novel treatments for chemotherapy-related side effects. (PsycInfo Database Record (c) 2026 APA, all rights reserved).