Developmental exposure to the SSRI citalopram causes long-lasting behavioural effects in the three-spined stickleback (Gasterosteus aculeatus)

Abstract

Selective Serotonin re-uptake inhibitors (SSRIs) are a class of psychotropic drugs used to treat depression in both adolescents and pregnant or breast-feeding mothers as well as in the general population. Recent research on rodents points to long-lasting behavioural effects of pre- and perinatal exposure to SSRIs which last into adulthood. In fish however, studies on effects of developmental exposure to SSRIs appears to be non-existent. In order to study effects of developmental SSRI exposure in fish, three-spine sticklebacks were exposed to 1.5 µg/l of the SSRI citalopram in the ambient water for 30 days, starting two days post-fertilisation. After approximately 100 days of remediation in clean water the fish were put through an extensive battery of behavioural tests. Feeding behaviour was tested as the number of bites against a piece of food and found to be increased in the exposed fish. Aggression levels were measured as the number of bites against a mirror image during 10 min and was also found to be significantly increased in the exposed fish. Novel tank behaviour and locomotor activity was tested in an aquarium that had a horizontal line drawn half-way between the bottom and the surface. Neither the latency to the first transition to the upper half, nor the number of transitions or the total time spent in the upper half was affected by treatment. Locomotor activity was significantly reduced in the exposed fish. The light/dark preference was tested in an aquarium where the bottom and walls were black on one side and white on the other. The number of transitions to the white side was significantly reduced in the exposed fish but there was no effect on the latency to the first transition or the total time spent in the white half. The results in the current study indicate that developmental SSRI exposure causes long-lasting behavioural effects in fish and contribute to the existing knowledge about SSRIs as environmental pollutants.

Impact of the antidepressant citalopram on the behaviour of two different life stages of brown trout

“…In addition, anxiolytic effects like reduced freezing behaviour in the novel tank diving test and increased curiosity in the novel object test were observed after exposure to 15 and 1.5 µg/L of citalopram respectively for 21 days. Whereas, Kellner et al (2017) exposed three-spined sticklebacks in a developmental stage for 30 days to 1.5 µg/L citalopram with a subsequent 120 days recovery phase and showed a reduced swimming activity in the novel tank diving test as well as increased aggressive behaviour. Though, neither freezing behaviour and latency or number of transitions spent in the upper half were influenced, which can be seen as no change in anxiety.…”

Study of the Effect of Administration of Citalopram on the Liver of the Pregnant Albino Rats and the Liver of their Offspring

“…The enzyme level of Aspartate Amino Transferase (AST), Alanine Aminotransferase (ALT) and Gamma Glutamyl Transpeptidase (GGT) in serum of the control albino rat mothers on the first and the fifteenth days after delivery were within normal range, these findings were the same as described by one study [23] . Citalopram used in this study as it was a psychotropic drug used to treat depression in pregnant or breast-feeding mothers as well as in the general population [24,25] .…”

Effects of monoamine manipulations on the personality and gene expression of three-spined sticklebacks

“…Concentrations of fluoxetine were chosen from previous work in fish and values recorded in ecological assessments of natural water (Fick et al, 2010;Silva et al, 2012;Eisenreich et al, 2017). Dosing was done concurrent with 40% water changes every 5 days to maintain the chosen concentrations (Benotti and Brownawell, 2009;Kellner et al, 2018). To prevent cross-contamination, each treatment had separate buckets and other tools needed for water change and redosing, color-coded to ensure that researchers remained blind to the treatment.…”

“…SSRI drugs inhibit the reuptake of the neurotransmitter serotonin from the synaptic cleft during signaling between neurons, by blocking the serotonin transporter; this results in serotonin remaining in the cleft for longer, prolonging the stimulation of serotonin receptors (Vaswani et al, 2003). Exposure to fluoxetine reduces aggression (Perreault et al, 2003;Bell et al, 2007;Clotfelter et al, 2007;Carere and Maestripieri, 2013;Eisenreich et al, 2017;Theodoridi et al, 2017;Barbosa et al, 2018;Kellner et al, 2018). Dopamine levels, polymorphisms in dopamine receptor and transporter genes, and differential methylation of dopamineassociated genes are related to novelty-seeking and exploratory behavior in mammals and birds (Schinka et al, 2002;Fidler et al, 2007;Egan et al, 2009;Filby et al, 2010;van Oers and Mueller, 2010;Shaw and Øverli, 2012;Caramaschi et al, 2013;Carere and Maestripieri, 2013;Holtmann et al, 2016;Abbey-Lee et al, 2018a).…”

“…Specifically, we focused on behavior describing variation in the personality traits exploration, aggression, sociability and boldness. Based on previous work, we predicted that our serotonin manipulation would increase serotonin levels in the brain, thus decreasing individual aggressiveness (Perreault et al, 2003;Bell et al, 2007;Clotfelter et al, 2007;Carere and Maestripieri, 2013;Eisenreich et al, 2017;Theodoridi et al, 2017;Barbosa et al, 2018;Kellner et al, 2018) and increasing boldness and exploration behavior (Egan et al, 2009). Our dopamine manipulation should increase dopamine receptor activity in the brain, and thus we predicted it would decrease exploration, boldness, aggressiveness and sociability (Schinka et al, 2002;Fidler et al, 2007;Egan et al, 2009;Filby et al, 2010;van Oers and Mueller, 2010;Carere and Maestripieri, 2013;Holtmann et al, 2016).…”