Selective serotonin re-uptake inhibitors in the environment Effects of citalopram on fish behaviour

Sammanfattning: Selective serotonin re-uptake inhibitors (SSRIs) are a class of anxiolytic and anti-depressant drugs. SSRIs act on the evolutionarily ancient serotonergic system which is virtually identical throughout the vertebrate phylum. Serotonin is involved in a wide range of processes ranging from neuronal and craniofacial embryonic development to regulation of behaviour. However, SSRIs are also emerging pollutants, mainly entering the environment via sewage treatment plants. Since the serotonergic system is virtually identical in humans and other animals, exposed animals will be affected in similar ways as humans and suspicions are rising that ecologically important behaviours may be affected in subtle ways. Using the three-spined stickleback (Gasterosteus aculeatus) and zebrafish (Danio rerio) as model organisms, this thesis focuses on the behavioural effects of SSRIs in fish. The SSRI used throughout this thesis is citalopram, which has been found in fish in coastal areas of the Baltic Sea and other parts of the world.Effects on behaviour were investigated using several different tests measuring stress response, feeding behaviour, aggression and locomotor activity. Anxiolytic effects of 0.1 μg/l, 1.5 μg/l 15 μg/l were investigated as well as effects of 0.15 μg/l and 1.5 μg/l on feeding behaviour. Because serotonin is involved in the development of the nervous system, the effects of developmental exposure to 1.5 μg/l was studied after 100 days of remediation. Finally, because SSRIs rarely occur alone in natural waters, the effects on zebrafish of citalopram in a cocktail scenario, with the anxiogenic compound 17α-ethinyl estradiol (EE2 ) was also investigated. Citalopram was found to have anxiolytic effects on the three-spined stickleback at 0.1 μg/l, 1.5 μg/l and 15 μg/l.Citalopram also suppressed feeding behaviour within a week of exposure and at concentrations as low as 0.15 μg/l. Developmental exposure to 1.5 μg/l for 30 days was found to increase aggression and feeding behaviour and to reduce locomotor activity. The changes were persistent and remained in adult fish. In the cocktail scenario, citalopram in single-substance exposure had anxiolytic effects on one parameter in the novel tank test at 0.1 μg/l. Citalopram enhanced the anxiogenic effects of EE2 in the novel tank test, but in the scototaxis test citalopram appeared to counteract the effects of EE2. It is concluded that citalopram has the potential to affect behaviour in fish at concentrations that have been found in close proximity of sewage treatment plants.