TY - JOUR

T1 - Acetic acid-induced pain elicits stress-, and camouflage-related responses in zebrafish: Modulatory effects of opioidergic drugs on neurobehavioral phenotypes

AU - Costa, Fabiano V.

AU - Gonçalves, Falco L.

AU - Borba , João V.

AU - Sabadin, Giovana R.

AU - Biasuz, Eduarda

AU - Santos, Laura W.

AU - Sneddon, Lynne U.

AU - Kalueff, Allan V.

AU - Rosemberg, Denis B.

N1 - The authors recognize the financial support and fellowships from Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) – Finance code 001 , Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS). D.B.R. is recipient of the CNPq Research Productivity Grant (Process no. 307690/2021-0 ) and his work is also supported by FAPERGS Programa Pesquisador Gaúcho – PQG Fellowship Grant (Process no. 19/2551-0001764-2) and PROEX/CAPES Fellowship Grant (Process no. 23038.002125/2021-85; Grant no. 0036/2021 ). This study is part of the National Institute of Science and Technology in 3D printing and Advanced Materials Applied to Human and Veterinary Health - INCT 3D-Saúde, funded by CNPq , Brazil (Grant no. 406436/2022-3 ). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the paper. A.V.K. is supported by St. Petersburg State University budgetary funds (Pure ID: 93020614 ). The laboratory partially used the facilities and equipment of the Resource Fund of Applied Genetics MIPT (support grant 075-15-2021-684 ).

PY - 2023

Y1 - 2023

N2 - 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. © 2023 Elsevier Inc.

AB - 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. © 2023 Elsevier Inc.

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U2 - 10.1016/j.cbpc.2023.109640

DO - 10.1016/j.cbpc.2023.109640

M3 - Article

VL - 270

JO - Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

JF - Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology

SN - 1532-0456

M1 - 109640

ER -