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

PLoS One. 2018 May 15;13(5):e0197259. doi: 10.1371/journal.pone.0197259. eCollection 2018.

Abstract

Metformin, the medicine most commonly prescribed for treatment of Type II diabetes, is among the most abundant pharmaceuticals being introduced into the environment. Pharmaceuticals are increasingly found in wastewater and surface waters around the world, often due to incomplete metabolism in humans and subsequent excretion in human waste. Risk analyses and exposure studies have raised concerns about potential negative impacts of pharmaceuticals at current environmental levels. Results of the present study indicate 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 adult male Betta splendens. Subjects exhibited less aggression toward a male dummy stimulus after four weeks exposure to metformin-treated water when compared to behavior 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 an even more substantial reduction 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aggression / drug effects*
  • Analysis of Variance
  • Animals
  • Behavior, Animal / drug effects
  • Dose-Response Relationship, Drug
  • Fishes*
  • Male
  • Metformin / toxicity*
  • Motor Activity / drug effects
  • Random Allocation
  • Water Pollutants, Chemical / toxicity*

Substances

  • Water Pollutants, Chemical
  • Metformin

Grants and funding

This study was supported in part by 2016 and 2017 Merrimack College Faculty Development Grants and the 2016 Murray Fellowship. All three forms of funding are internal and include no grant numbers or funds from external sources requiring references to funder's websites. The funders (Merrimack College) had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.