Ketamine is a non-competitive glutamatergic antagonist that induces analgesia and anesthesia. Although ketamine displays anxiolytic and antidepressant properties, it may induce pro-psychosis and hallucinogen effects, as well as stereotypic behaviors following acute administration at sub-anesthetic doses. Since heightened aggression is maladaptive and may comorbid with various neuropsychiatric disorders, we aimed to investigate whether ketamine modulates aggressive behavior in adult zebrafish. Fish were acutely exposed to 2, 20, and 40 mg/L ketamine for 20 min and their locomotion, exploratory activity, and aggression towards mirror were further assessed. Ketamine (2 mg/L) increased aggression-related phenotypes, while 20 and 40 mg/L reduced aggression and elicited stereotypic behaviors by causing hyperlocomotion, altering motor patterns, and increasing circling behavior at the higher concentration tested. Collectively, our data expand the utility of zebrafish models to investigate the influence of sub-anesthetic concentrations of ketamine on aggression behavior domain in translational neuropsychiatric research field.

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Zidovudine (AZT) is the most commonly prescribed antiviral drug for the treatment of human immunodeficiency virus (HIV) infection. However, its chronic administration causes toxic side effects limiting its use. This study aimed to evaluate the toxicity of different concentrations of AZT and novel chalcogen derivatives (7A, 7D, 7G, 7K, 7M) on locomotion, mitochondrial dysfunction, acetylcholinesterase (AChE) activity, and production of reactive oxygen species (ROS) in adult Drosophila melanogaster. Our results show that AZT and its derivative 7K at a concentration of 10 μM impaired flies' locomotor behavior. Furthermore, AZT and the derivatives 7K, 7A, and 7M induced mitochondrial dysfunction observed by a decrease in oxygen flux through mitochondrial complexes I and II. Neither of the compounds tested affected AChE activity or ROS production in flies. According to these data, AZT derivatives presented the following decreasing order of toxicity: 7K > AZT > 7G > 7A > 7M > 7D. Based on the chemical structure, it is possible to infer that the presence of the seleno‐phenyl group in 7A and 7G increases their toxicity compared to compounds 7D and 7M. In addition, compounds 7G, 7M, and 7K with three carbon atoms as spacer were more toxic than analogs containing one carbon atom (7A and 7D). Finally, the insertion of a p‐methoxyl group enhances toxicity (7K). Based on these results, excepting 7K, all other chalcogen derivatives presented lower toxicity than AZT and are potential drug candidates.