Environmental concentrations of metformin exposure affect aggressive behavior in male Siamese fighting fish, Betta splendens

Background/Question/Methods: Pharmaceuticals among other medications are found in waste- and surface waters around the world in increasing concentrations due to incomplete metabolism in humans and excretion in waste. These chemicals become part of wastewater treatment plant (WWTP) effluent released into local surface waters including streams, rivers, and coastal estuaries. A growing body of research has raised concerns about potential negative impacts of such pharmaceuticals at current environmental levels. Metformin, the medicine most commonly prescribed by doctors worldwide for the treatment of Type II diabetes, is among the most abundant pharmaceuticals being introduced into the environment. These levels will likely continue to rise given its use as a treatment option for a broadening variety of health problems from cancers to polycystic ovarian syndrome and the staggering rate of increase in diabetes diagnoses in recent decades. Although the effects of pharmaceuticals on wildlife have received increased attention in the literature in recent years, metformin’s impact on aquatic life is poorly understood. To date, no one has addressed the effects of metformin exposure on the behavior of aquatic life. Many animals may experience maladaptive behavioral changes as a consequence of chemical exposure even in the absence of obvious morphological effects. The Siamese fighting fish (Betta splendens) has become a model organism for studies addressing the physiological and behavioral effects of chemical exposure, as males of the species exhibit discrete and stereotyped aggressive behaviors in defending their territories against conspecific rivals.

Results/Conclusions: Results of the present study show that metformin at concentrations in the range of what has been documented in freshwater systems and waste-water effluent (40 µg/L) affects aggressive behavior in B. splendens. Metformin-exposed males exhibited less aggression toward a male conspecific stimulus after four weeks when compared to levels measured immediately prior to their exposure, and in comparison to a separate cohort of un-exposed control fish. This effect persisted after 20 weeks exposure as well. Subjects exposed to metformin at a concentration twice that currently observed in nature (80 µg/L) exhibited even more substantial reductions in aggressive behaviors compared to controls and pre-exposure measurements than those observed in the low-dose treatment group. Such changes in behavior have the potential to affect male fitness and possibly impact the health of natural populations of aquatic organisms exposed to the drug.