Exposure to the pharmaceutical buspirone alters locomotor activity, anxiety-related behaviors, and transcripts related to serotonin signaling in larval zebrafish (Danio rerio)

Neurotoxicol Teratol. 2024 Jan-Feb:101:107318. doi: 10.1016/j.ntt.2023.107318. Epub 2024 Jan 2.

Abstract

Buspirone is a pharmaceutical used to treat general anxiety disorder by acting on the dopaminergic and serotoninergic system. Buspirone, like many human pharmaceuticals, has been detected in municipal wastewater; however, the environmental exposure risks are unknown for this psychoactive compound. We studied the effects of buspirone on the behavior of zebrafish, focusing on locomotor and anxiolytic behavior. We also measured transcripts associated with oxidative stress, neurotoxicity, and serotonin signaling to identify potential mechanisms underlying the behavioral changes. Concentrations ranged from environmentally relevant (nM) to physiologically active concentrations typical of human pharmaceuticals (μM). Buspirone treatment did not impact survival, nor did it induce deformities in zebrafish treated for 7 days up to 10 μM. There was a positive relationship between locomotor activity and buspirone concentration in dark periods of the visual motor response test. In the light-dark preference test, both the average time per visit to the dark zone and the percent cumulative duration in the dark zone were increased by 1 μM buspirone. Transcript levels of ache, manf, and mbp were decreased in larvae, while the expression of gap43 was increased following exposure to buspirone, indicating potential neurotoxic effects. There was also reduced expression of serotonin-related genes encoding receptors, transporters, and biosynthesis enzymes (i.e., 5ht1aa, sertb, and tph1a). These data increase understanding of the behavioral and molecular responses in zebrafish following waterborne exposure to neuroactive pharmaceuticals like buspirone.

Keywords: Anxiety; Aquatic toxicology; Behavior; Pharmaceutical; Serotonin.

MeSH terms

  • Animals
  • Anxiety / chemically induced
  • Anxiety Disorders*
  • Behavior, Animal
  • Buspirone* / metabolism
  • Buspirone* / pharmacology
  • Humans
  • Larva
  • Locomotion
  • Pharmaceutical Preparations / metabolism
  • Serotonin / metabolism
  • Zebrafish* / metabolism

Substances

  • Buspirone
  • Serotonin
  • Pharmaceutical Preparations

Supplementary concepts

  • general anxiety disorder