Grant: Discovery Grants Program - Individual

We focus on two areas of fish physiology: analgesics and their side effects. Analgesia: The goal here is to understand the ways that fish respond to a noxious (?painful?) stimulus and how drugs modify that response. Life science researchers in Canada use as many fish as either rats or mice. The Canadian Council for Animal Care (CCAC) ?Guidelines for Use of Fish in Research? does not contain specific recommendations for the use of analgesics (?pain killers?) because we do not have sufficient information to make the appropriate recommendations. Our laboratory tests some fundamental assumptions regarding analgesics and analgesia in fish. We develop tests that can be used to produce dose-response curves (that is, how much drug is required to get an effect) for analgesics and measure how long they are effective. We have done this for morphine and now propose to do it for other analgesics. The question of whether or not fish can ?feel pain? is a very difficult one. In our experiments, we look for a response to a stimulus that would be considered painful to humans or other mammals. Here we propose to study the effect of sea lice and the wounds they cause on fish behavior and see if the behavior is modified by local anesthetics, if behavior is modified by substances secreted by the sea lice, and if so, the mechanisms the sea lice use to modify the fish behavior. We also will test the effects of analgesics on fish behavior associated with wounds that occur when implanting telemetry devices. This work is important because it likely will influence CCAC policy. Side effects of local anesthetics ? their effects on mitochondrial energetics. It has been known for some time that systemic administration of local anesthetics results in cytotoxic side effects, especially on cardiac tissue and nervous tissue. Different mechanisms have been proposed for the cytotoxic effects, but most evidence points to the effect being at the mitochondrial level. The mitochondrion is the organelle present in all cells that is responsible for supplying energy in the form of ATP for that cell to balance its energy use in order to support cell function. Previous studies show that local anesthetics depress aerobic respiration of mitochondria and cells. My overall aim in these experiments is to measure the effects of local anesthetics on cell and mitochondrial energetics from fish tissues and to unveil the mechanisms accounting for their effects. I will focus on three local anesthetics: lidocaine and bupivacaine (because these are the drugs that have been suggested by veterinarians and other researchers that we use with fish) and tricaine (because this is the drug most often used to anesthetize fish).