Evaluation of Intramuscular Use of Medetomidine (Alpha-2 Adrenergic Agonist) as an Alternative to Tricaine Methanesulfonate (MS-222, Finquel®) for Sedation and Anesthesia in Teleosts and Elasmobranchs
The current standard for fish immersion anesthesia and sedation, tricaine methanesulfonate (MS-222), provides a safe and effective means of immobilization and anesthesia for teleosts. A safe, effective intramuscularly injected anesthetic agent would be desirable in cases such as field studies, when equipment for continuous infusion of anesthetic solutions over the gills is unavailable, or when the size of the fish makes bath exposure impractical.
No controlled studies on the efficacy of intramuscular medetomidine for teleost and elasmobranch sedation or anesthesia have been published, and the few anecdotal reports on their use have provided very mixed reviews. This study's goal was to evaluate the efficacy of intramuscular administration of the alpha-2 agonist, medetomidine, as an alternative to anesthesia and sedation with MS-222. We used comet goldfish (Carassius auratus) and chain dogfish (Scyliorhinus retifer) as the teleost and elasmobranch models respectively.
Different teleost and elasmobranch subjects were systematically injected intramuscularly with medetomidine beginning at 50 mcg/kg, increasing to 100 mcg/kg, and increasing in 100 mcg/kg increments thereafter to a high dose of 1,000 mcg/kg (elasmobranchs) to 1,200 mcg/kg (teleosts) in order to determine an effective dose. A control subject was injected with an equal volume of saline at the time each subject was injected with drug. After injection, controls and subjects were monitored for changes in respiration, activity, posture in the water column, degree of resistance to visual and tactile stimulation, and righting ability when inverted. In no subject was a surgical plane of anesthesia (unresponsive to aversive stimuli) achieved within this dose range. While no effect was noted in teleosts at lower doses, high doses (~12X the recommended mammalian dose) yielded moderate sedation, as evidenced by slowed respiratory rates, a decrease or cessation of swimming behavior, listing, and much decreased response to visual and tactile stimulation. Elasmobranch subjects responded similarly in terms of respiration and activity, however the degree of sedation, even at ~10X the recommended mammalian dose, was minimal; animals exhibited decreased respiratory rates, and activity, but maintained the ability to respond to all visual and tactile stimuli. Intramuscular administration of the alpha-2 antagonist, atipamezole, to teleost subjects at their maximum point of sedation provided consistent reversal of sedation effects within 15 minutes. These data suggest that while medetomidine provides only minimal sedation in elasmobranchs at the studied doses, it is a useful, safe, and reversible sedative for teleost subjects. Though medetomidine will not replace MS-222 for teleosts, its administration may facilitate physical examinations, injections, blood draws, animal handling and transport in teleost subjects in instances where MS-222 is unavailable or undesirable, and may provide minimal sedation in elasmobranchs that could be useful during transport.
A comparison of the amino acid sequences of putative agonist and antagonist binding regions of mammalian and teleost alpha-2a receptors offers a possible explanation for the decreased efficacy of medetomidine in fish. An examination of amino acid sequences of cloned alpha-2a receptors of mammals and teleosts on the Entrez Nucleotides Database with the Megalign DNA comparison software reveals that overall amino acid identity between these vertebrate classes is low (approximately 58 percent). Studies have shown that even single amino acid differences in regions of the alpha-2a receptor believed to be involved in ligand binding dramatically alter receptor-drug affinity. A decrease in binding affinity of a ligand for a specific receptor often requires a substantial increase in the amount of ligand required to reach a similar or decreased result. Thus, the decrease in medetomidine efficacy in fish compared to mammals could result from the dissimilarities in ligand binding regions of alpha-2a receptor protein sequences.