ABSTRACT
The zebrafish has been considered an ideal model for studies of complex behaviors since its behavioral repertoire is well described. Therefore, this study evaluated the perceived pain through behavioral changes in zebrafish larvae. Here we investigated the Acetic Acid (AA) effects on zebrafish larvae exposed in a short-time period (60 s) and the preventive effect from routinely used compounds, Dimethyl Sulfoxide (DMSO), Ethanol (EtOH), Ibuprofen (IBP), and Paracetamol (PAR). In addition, the effect of P2×7 antagonist, A740003, and pannexin channel 1 (PANX-1) inhibitor Probenecid (PROB) on AA-induced behavioral changes were evaluated. AA impaired the distance covered, acceleration, movement, and latency to the first entry in the center from 5 dpf exposed larvae. At 0.050% AA, PAR prevented alterations from the distance covered, acceleration, and movement. Surprisingly, 0.3% DMSO prevented behavioral changes induced by AA. However, the effects from 0.2% DMSO were not prominent. We used 0.2% DMSO as a PROB diluent. PROB prevented the changes in distance and movement observed at both AA concentrations (0.0025% and 0.05%) tested. Since EtOH had no analgesic properties, we used it as an A740003 vehicle to observe the analgesic effects of this compound. As noted, A740003 did not prevent the behavioral changes in the AA-induced pain model. In contrast, 0.2% DMSO and PROB prevented AA-induced behavioral changes. These data enforce that zebrafish could be used in translational studies since this species has behavioral responses related to pain in the early stages of development and responses to analgesics similar to observed in mammals.
Subject(s)
Analgesics/pharmacology , Behavior, Animal/drug effects , Connexins , Dimethyl Sulfoxide/pharmacology , Pain , Purinergic P2X Receptor Antagonists/pharmacology , Receptors, Purinergic P2X7 , Zebrafish Proteins , Animals , Connexins/antagonists & inhibitors , Connexins/metabolism , Disease Models, Animal , Larva , Pain/drug therapy , Pain/metabolism , Receptors, Purinergic P2X7/metabolism , Zebrafish , Zebrafish Proteins/antagonists & inhibitors , Zebrafish Proteins/metabolismABSTRACT
Oxytetracycline (OTC) is one of the broad-spectrum antibiotics widely used for the treatment of fish-farm infection. Considering that behavior is directly related to reproduction, individual fitness, and survival, it is important to evaluate the impact of antibiotics on the behavioral repertoire in fish. Zebrafish (Danio rerio) presents a well-described behavioral repertoire to reliably demonstrate complex responses to chemical compound exposure. This work aims to identify the role of OTC in comprehensive behavioral parameters and whole-body cortisol levels in adult zebrafish. Here we report that OTC exposure (10, 20, and 100 mg/L) induces an anxiogenic-like phenotype in the novel tank test. OTC exposure also changes the behavior of social interaction with a shoal of unknown zebrafish - characterized as a stimulus group. Zebrafish exposed to OTC (10 mg/L) remains a longer period in the stimulus zone when compared to the control group. Clonazepam (0.006 mg/L) was able to reverse anxiogenic-like behavior and the changes in social behavior induced by OTC. We also demonstrated that cortisol levels were significantly decreased after exposure to OTC (10, 20, and 100 mg/L), which were not reversed by clonazepam. These findings highlight the growing utility of zebrafish as a model to understand the impact of antibiotics on behavior and their underlying mechanisms.