Acetic acid-induced pain elicits stress-, and camouflage-related responses in zebrafish: Modulatory effects of opioidergic drugs on neurobehavioral phenotypes

Fabiano V. Costa*, Falco L. Gonçalves, João V. Borba, Giovana R. Sabadin, Eduarda Biasuz, Laura W. Santos, Lynne U. Sneddon, Allan V. Kalueff, Denis B. Rosemberg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

While pain results from the activation of nociceptors following noxious stimuli, mounting evidence links pain- and stress-related responses in mammals. In zebrafish, the activation of hypothalamic-pituitary-interrenal (HPI) axis may also regulate body pigmentation (the camouflage response). Here, we aimed to investigate a putative relationship between pain-, stress-, and camouflage-related parameters in adult zebrafish. To answer this question, we assessed whether intraperitoneal acetic acid injection can activate the HPI axis, measuring whole-body cortisol and the camouflage response as physiological endpoints in the presence or absence of morphine or naloxone, an opioid antagonist. Acetic acid induced a stereotypic circling behavior in the top of the tank, accompanied by abdominal writhing-like response, a specific phenotype that reflects local nociceptive effect. Both whole-body cortisol levels and camouflage response increased in the acetic acid group, while morphine prevented these responses, and naloxone antagonized morphine-induced effects. Moreover, we observed positive correlations between representative behavioral, physiological and skin coloration endpoints, and a “pain index” was proposed to summarize phenotypic profile of zebrafish under different pharmacological manipulations. Collectively, these findings suggest a coordinated activation of pain, camouflage- and stress-related pathways following acetic acid injection in zebrafish. Our data also support that camouflage response represents a novel and relevant biomarker for future probing pain and stress neurobiology, with a robust sensitivity to opioidergic drugs.

Original languageEnglish
Article number109640
JournalComparative Biochemistry and Physiology - C Toxicology and Pharmacology
Volume270
DOIs
Publication statusPublished - Aug 2023
Externally publishedYes

Keywords

  • Body pigmentation
  • Opioid system
  • Pain-like phenotypes
  • Stress
  • Zebrafish

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