John Wiley & Sons, Ltd.

Anti‐anxiety drugs and fish behaviour: Establishing the link between internal concentrations of oxazepam and behavioural effects

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Psychoactive drugs are frequently detected in the aquatic environment. The evolutionary conservation of the molecular targets of these drugs in fish suggest that they may elicit mode‐of‐action mediated effects in fish as they do in humans, and one the key open question is at what exposure concentrations these effects might occur. In the present study, we investigated the uptake and tissue distribution of the benzodiazepine oxazepam in the fathead minnow (Pimephales promelas) after 28 days of waterborne exposure to 0.8, 4.7, and 30.6 µg L−1. Successively, we explored the relationship between the internal concentrations of oxazepam and the effects on fish exploratory behaviour quantified by performing two types of behavioural tests, the Novel Tank Diving Test and the Shelter‐seeking Test. The highest internal concentrations of oxazepam were found in brain, followed by plasma and liver, whereas muscle presented the lowest values. Average concentrations measured in the plasma of fish from the three exposure groups were, respectively, 8.7 ± 5.7, 30.3 ± 16.1, and 98.8 ± 72.9 µg L−1.Significant correlations between plasma and tissue concentrations of oxazepam were found in all three groups. Exposure of fish to 30.6µg L−1 in water produced plasma concentrations within or just below the Human Therapeutic Plasma Concentration (HTPC) range in many individuals. Statistically significant behavioural effects in the Novel Tank Diving test were observed in fish exposed to 4.7µg L−1. In this group, plasma concentrations of oxazepam were approximately one third of the lowest HTPC value. No significant effects were observed in fish exposed to the lowest and highest concentrations. The significance of these results is discussed in the context of the species‐specific behaviour of fathead minnow and existing knowledge of oxazepam pharmacology. This article is protected by copyright. All rights reserved

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