| Summary: | ABSTRACT Growth of marine organisms, fouling, on man-made constructions submerged in the water is regarded as a major problem. For vessels, fouling increases drag and thereby fuel consumption, wherefore antifouling paints are used. Traditionally, they contain toxic compounds, and several of these have unwanted effects in the environment. Today the search for environmentally acceptable and efficient alternatives is intense. Medetomidine, originally used as a veterinary sedative, inhibits barnacle settling at nanomolar concentrations. It is presently under evaluation for use as an antifouling agent. The studies within this thesis were performed to investigate medetomidine responses in fish. The focus was to identify early effects, occurring from low concentrations. Studies have been performed in the species rainbow trout, Atlantic cod, turbot, Atlantic salmon and three spined stickleback. Exposure time vary from 1 up to 54 days, and a set of parameters have been investigated including biochemical biomarkers, growth and related parameters, behaviour and large scale gene expression. Paleness is the most obvious effect of medetomidine in fish and appears from 0.5 to 50 nM, depending on species. Colour was observed and quantified, and the function of melanophores (pigment cells) after long term exposure to medetomidine was investigated. It is suggested that melanophores are functional after treatment, and thus the colour change may be reversible. Although not lethal per-see, paleness may have consequences for fish predator-prey interactions (camouflage), social signalling and UV protection. Medetomidine also showed to affect the activity of the hepatic enzyme Cytochrome P4501A (CYP1A), measured as EROD activity. A minor increase in activity was observed in vivo in several of the investigated species. In vitro, medetomidine showed instead to be a potent inhibitor of EROD activity with median inhibition values (IC50) in the nanomolar range. An inhibited CYP1A activity may interfere with fish detoxification of toxicants ...
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