Long-term treatment with 3-nitropropionic acid (3-NPA), a toxin derived from plants and fungi, may reproduce symptoms and biochemical characteristics of Huntington's disease (HD). Our study evaluated the effects of 3-NPA on the physiological and behavioral responses in zebrafish larvae and adults. Larvae exposed to 0.1, 0.2, or 0.5 mM 3-NPA exhibited an increase in heart rate at 2- and 5-days post-fertilization (dpf). There was a decrease in the ocular distance at 5 dpf with 0.05 mM 3-NPA treatment. However, 3-NPA did not alter larval locomotor parameters. Adult zebrafish received 3-NPA intraperitoneal injections (a total of seven injections at doses 10, 20, or 60 mg/kg every 96 h) and showed a decrease in body weight , locomotion and aggressive behavior. No changes were observed in anxiety-like behavior and social interaction between 3-NPA-exposed animals and control groups. However, 3-NPA-treated animals (at 60 mg/kg) demonstrated impaired long-term aversive memory. Overall, 3-NPA exposure induced morphological and heart rate alterations in zebrafish larvae. Additionally, our study showed behavioral changes in zebrafish that were submitted to long-term 3-NPA treatment, which could be related to HD symptoms.
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