Long-term exposure to cyprodinil causes abnormal zebrafish aggressive and antipredator behavior through the hypothalamic-pituitary-interrenal axis.

Cyprodinil, one of the main pyrimidinamine fungicides, has been used to control fungal diseases in plants and vegetables worldwide. Previous studies have investigated the influences of cyprodinil on the developmental and reproductive toxicity of fish. However, it remains unknown whether it affects fish behaviors and the underlying mechanisms. In our current study, zebrafish, an ideal model animal for behavioral studies, were exposed to cyprodinil from fertilization to 240 days postfertilization at 0.1 μg/L (environmentally relevant concentration) and 1, 10 μg/L. Firstly, we observed that aggressive behavior of zebrafish was significantly enhanced after exposure to 0.1-10 μg/L cyprodinil and antipredator behavior was decreased after exposure. Cyprodinil exposure altered the adrenocorticotropic hormone and cortisol levels, which regulate cortisol homeostasis and were significantly reduced in all exposure groups (0.1-10 μg/L). In addition, most of the key genes in the hypothalamic-pituitary-interrenal gland axis, such as corticotropin-releasing hormone and melanocortin 2 receptor, were downregulated significantly in all exposure groups, which was consistent with the hormone levels. In addition, in the hypothalamus, the number of apoptotic cells increased in a dose-dependent manner in the cyprodinil exposure groups. Moreover, these changes were potentially responsible for the increased aggression of zebrafish during the mirror-like aggressive test and for the reduced antipredator behavior during the predator avoidance test. Overall, the data provided herein further our understanding of cyprodinil toxicity and can be used to assess the ecological effects of cyprodinil on the induction of abnormal behaviors at the environmental level.