Physiological Endpoints for Potential SSRI Interactions in Fish

Abstract

Selective serotonin reuptake inhibitors (SSRIs) are among the pharmaceutical compounds frequently detected in sewage treatment plant effluents and surface waters, albeit at very low concentrations, and have therefore become a focus of interest as environmental pollutants. These neuroactive drugs are primarily used in the treatment of depression but have also found broader use as medication for other neurological dysfunctions, consequently resulting in a steady increase of prescriptions worldwide. SSRIs, via inhibition of the serotonin (5-hydroxytryptamine, 5-HT) reuptake mechanism, induce an increase in extracellular 5-HT concentration within the central nervous system of mammals. The phylogenetically ancient and highly conserved neurotransmitter and neurohormone 5-HT has been found in invertebrates and vertebrates, although its specific physiological role and mode of action is unknown for many species. Consequently, it is difficult to assess the impact of chronic SSRI exposure in the environment, especially in the aquatic ecosystem. In view of this, the current knowledge of the functions of 5-HT in fish physiology is reviewed and, via comparison to the physiological role and function of 5-HT in mammals, a characterization of the potential impact of chronic SSRI exposure on fish is provided. Moreover, the insight on the physiological function of 5-HT strongly suggests that the experimental approaches currently used are inadequate if not entirely improper for routine environmental risk assessment of pharmaceuticals (e.g., SSRIs), as relevant endpoints are not assessed or impossible to determine.

Prozac in the water: Chronic fluoxetine exposure and predation risk interact to shape behaviors in an estuarine crab

“…We also found that extended exposure to fluoxetine exacerbated the effect on risk behaviors, as crabs in the 30 ng/L group were most likely to engage in risk activity following 7–9 weeks of exposure. Perhaps this is due to bioconcentration of the drug in animal tissue as fluoxetine hydrochloride is a lipophilic compound (Kreke & Dietrich, 2008). Interestingly, there was little difference between diurnal and nocturnal activity levels in crabs exposed to 3 ng/L of fluoxetine.…”

“…Fluoxetine is one of the most widely used antidepressants in the world (Ankley et al., 2007; Brooks et al., 2003) and a large amount of research has documented its occurrence in aquatic (Bringolf et al., 2010; Corcoran et al., 2010; Kwon & Armbrust, 2006; Ramirez et al., 2009) and marine (Kreke & Dietrich, 2008; Vasskog et al., 2008) environments. With growing human populations in coastal zones, increasing use of antidepressants like fluoxetine is expected, suggesting higher future concentrations in the marine environment.…”

“…To address this data gap, we conducted a laboratory study to assess how predator presence and prolonged exposure to the pharmaceutical contaminant fluoxetine interact to shape risk behaviors among the shore crab, Hemigrapsus oregonensis . Fluoxetine has been frequently detected in coastal areas at low concentrations (0.03–300 ng/L; Kreke & Dietrich, 2008; Vasskog et al., 2008) and is considered toxic to fish and marine invertebrates at high concentrations (Brooks et al., 2003). We were interested in the role of fluoxetine as a persistent ecological stressor in estuaries where sublethal concentrations between 3 and 30 ng/L are commonly detected (Kreke & Dietrich, 2008; Vasskog et al., 2008).…”

“…Fluoxetine has been frequently detected in coastal areas at low concentrations (0.03–300 ng/L; Kreke & Dietrich, 2008; Vasskog et al., 2008) and is considered toxic to fish and marine invertebrates at high concentrations (Brooks et al., 2003). We were interested in the role of fluoxetine as a persistent ecological stressor in estuaries where sublethal concentrations between 3 and 30 ng/L are commonly detected (Kreke & Dietrich, 2008; Vasskog et al., 2008). We conducted a series of diurnal and nocturnal behavioral trials over 9 weeks to assess whether fluoxetine exposure altered risk behaviors of H. oregonensis in response to a predator, the red rock crab Cancer productus .…”

Ecological effects of pharmaceuticals in aquatic systems—impacts through behavioural alterations

“…Serotonin levels influence both physiology [60] and behaviour in a wide range of organisms, including fish [61,62], and play a pivotal role in activity, aggression and reproductive behaviours [62][63][64], which has been shown, for example, by a negative correlation between serotonin levels and levels of aggression [65,66]. It is therefore intuitive to use behavioural endpoints when studying effects of SSRIs and SNRIs, and several studies have evaluated impacts on various behaviours in fish (table 2).…”