Sedative options for fish research: a brief review with new data on sedation of warm-, cool-, and coldwater fishes and recommendations for the drug approval process

Abstract

The absence of a suitable sedative allowing treated fish to be released immediately after recovery constrains research and poses a risk to fish and those handling them. The U.S. Food and Drug Administration’s reliance on multi-taxon datasets represents a major hurdle in the approval process. Experiments were conducted with twelve freshwater taxa to assess time to induction and recovery of fish sedated with different doses of AQUI-S 20E (10 % eugenol), Benzoak (20 % benzocaine), or MS-222 (99.5 % tricaine methanesulfonate) administered under various conditions. A retrospective analysis was conducted to determine whether sedative dose, water temperature, dissolved oxygen concentration, and fish length or weight contributed to variation in induction and recovery times. A subsequent experiment with eugenol was conducted to further assess time to sedation as a function of water temperature and sedative dose. Generally, higher doses and warmer temperatures were associated with faster inductions. Warmer temperatures were also associated with more rapid recoveries, however, high doses tended to delay recovery. Positive relationships linking estimated respiration rates and times to induction and recovery suggest the effects of temperature and body size on sedation timing may be a function of oxygen consumption. Collectively, our results demonstrated that the response of fish to chemical sedatives is primarily a function of sedative dose and water temperature, and, to a lesser extent, fish size and dissolved oxygen, not taxonomic classification. Accordingly, we suggest that as much information could be gained from a single taxon evaluated under different conditions as experiments involving multiple fishes. We recommend those establishing data requirements for fish drug approvals review these findings and consider alternative experimental designs as means of addressing regulatory requirements more efficiently and with greater rigor.