Antidepressants in Surface Waters: Fluoxetine Influences Mosquitofish Anxiety-Related Behavior at Environmentally Relevant Levels

Abstract

Pharmaceutical contamination is an increasing problem globally. In this regard, the selective serotonin reuptake inhibitors (SSRIs)a group of antidepressantsare particularly concerning. By disrupting the serotonergic system, SSRIs have the potential to affect ecologically important behaviors in exposed wildlife. Despite this, the nature and magnitude of behavioral perturbations resulting from environmentally relevant SSRI exposure among species is poorly understood. Accordingly, we investigated the effects of two field-realistic levels of the SSRI fluoxetine (61 and 352 ng/L) on sociability and anxiety-related behaviors in eastern mosquitofish (Gambusia holbrooki) for 28 days. Additionally, we measured whole-body tissue concentrations of fluoxetine and norfluoxetine. We found that fluoxetine altered anxiety-related behavior but not sociability. Specifically, female fish showed reduced anxiety-related behavior at the lower treatment level, while males showed an increase at the higher treatment level. In addition, we report a biomass-dependent and sex-specific accumulation of fluoxetine and norfluoxetine, with smaller fish showing higher relative tissue concentrations, with this relationship being more pronounced in males. Our study provides evidence for nonmonotonic and sex-specific effects of fluoxetine exposure at field-realistic concentrations. More broadly, our study demonstrated that neuroactive pharmaceuticals, such as fluoxetine, can affect aquatic life by causing subtle but important shifts in ecologically relevant behaviors.

Field-realistic antidepressant exposure disrupts group foraging dynamics in mosquitofish

“…The primary target molecule of fluoxetine (the serotonin transport molecule) is conserved across all vertebrate taxa [7], and, thus, fluoxetine has the potential to affect a diverse array of ecologically important behaviours in wildlife [8,9]. Indeed, there is growing evidence that antidepressants, such as fluoxetine, can disrupt a range of behaviours in non-target species at environmentally relevant concentrations, such as activity [10][11][12][13], anxiety [14][15][16], predator avoidance and escape [17][18][19][20], and foraging [21,22]. However, to date, few studies have considered how impacts of psychoactive pollutants might be affected by social context [23,24], and fewer still have directly asked whether impacts seen in social isolation are reflective of those in a social context [25].…”

Impacts of Psychopharmaceuticals on the Neurodevelopment of Aquatic Wildlife: A Call for Increased Knowledge Exchange across Disciplines to Highlight Implications for Human Health

“…We are all familiar with the canary in the coal mine, and thus the idea that animal species can serve as potential indicators of environmental hazards and impending threats to public health is not new [ 57 ]. While the impact of pharmaceutical contamination on animal behavior is of particular concern to ecologists and conservation biologists [ 28 , 29 , 31 , 42 , 45 , 58 ], we postulate that equal concern should be placed on the potential effects of these substances on human neurodevelopment, and their relationship to biobehavioral disturbances and psychiatric conditions. In addition, we believe that the adverse effects of environmental pollutants on aquatic organisms—most notably in fish—are extremely relevant to a wide range of human health professionals (e.g., physicians, scientific investigators, child psychiatrists, policymakers, and public health officials concerned with gestational health and neurodevelopment).…”

“…The adverse effects of SSRIs on physiology and neurodevelopment have been particularly well studied in fish. Numerous studies have demonstrated that fish exposed to a wide range of environmentally relevant concentrations of SSRIs or other antidepressants exhibit substantial physiological and neurological changes in a sex- and dose-dependent manner [ 31 , 39 , 40 , 41 , 42 , 43 , 44 , 45 ]. The observed effects of antidepressants in fish include: changes in behavior (e.g., mating behavior, predator avoidance, anxiety, and aggression); substantial developmental and physiological abnormalities; changes in sexual selection, growth, and sperm count; and mortality.…”

Toward a theory of ecosystem well-being

“…Additionally, negative mental and social experiences can also be indicated via biomarkers of stress. A measure of stress, anxiety has been compared time and again in humans and non-human animals for the purpose of understanding if pharmaceutical drugs can help humans, i.e., mechanisms underlying responses in non-human animal models are extrapolated to human subjects (e.g., Groenink et al, 2015;Holsboer & Ströhle, 2005;Martin, 1998;Schmidt & Muller, 2006;Treit, 1985), but non-target anxiety-related behavior has also been documented in fish exposed to environmentally relevant concentrations of antidepressants intended for humans (Martin, 2019). Application of these studies, usually of rodents, might be used for consideration of ecosystem well-being, e.g., instead, outcomes to non-human test-subjects can be considered relative to their own health and well-being.…”