Development of an opioid self-administration assay to study drug seeking in zebrafish

Bossé, Gabriel D.; Peterson, Randall T.

doi:10.1016/j.bbr.2017.08.001

Cited by 50 publications

(37 citation statements)

References 67 publications

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“…Previous studies have only explored the effects of naloxone for up to 60 min after administration in zebrafish (e.g. Bosse and Peterson, 2017;Costa et al, 2019b); thus, future studies should explore the duration of action in fish. In mammals, naloxone has a short duration of action (∼15-30 min), requiring re-administration in cases of opioid overdose (Gerak et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

Acute and chronic stress prevents responses to pain in zebrafish: evidence for stress-induced analgesia

Thomson

Deakin

Cossins

et al. 2020

Journal of Experimental Biology

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The state of an animal prior to the application of a noxious stimulus can have a profound effect on their nociceptive threshold and subsequent behaviour. In mammals, the presence of acute stress preceding a painful event can have an analgesic effect whereas the presence of chronic stress can result in hyperalgesia. While considerable research has been conducted on the ability of stress to modulate mammalian responses to pain, relatively little is known about fish. This is of particular concern given that zebrafish (Danio rerio) are an extensively used model organism subject to a wide array of invasive procedures where the level of stress prior to experimentation could pose a major confounding factor. This study, therefore, investigated the impact of both acute and chronic stress on the behaviour of zebrafish subjected to a potentially painful laboratory procedure, the fin clip. In stress-free individuals, those subjected to the fin clip spent more time in the bottom of the tank, had reduced swimming speeds and less complex swimming trajectories; however, these behavioural changes were absent in fin-clipped fish that were first subject to either chronic or acute stress, suggesting the possibility of stress-induced analgesia (SIA). To test this, the opioid antagonist naloxone was administered to fish prior to the application of both the stress and fin-clip procedure. After naloxone, acutely stressed fin-clipped zebrafish exhibited the same behaviours as stress-free fin-clipped fish. This indicates the presence of SIA and the importance of opioid signalling in this mechanism. As stress reduced nociceptive responses in zebrafish, this demonstrates the potential for an endogenous analgesic system akin to the mammalian system. Future studies should delineate the neurobiological basis of stress-induced analgesia in fish.

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Section: Discussionmentioning

confidence: 99%

Acute and chronic stress prevents responses to pain in zebrafish: evidence for stress-induced analgesia

Thomson

Deakin

Cossins

et al. 2020

Journal of Experimental Biology

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“…These neuroactive steroids have been shown to affect neuronal activity by binding to different neurotransmitters receptors including key pathways relevant to substance abuse such as glutamatergic (NMDA), GABAergic and dopaminergic systems [64][65][66] . The modulation of these pathways has been shown to be important in the regulation of opioid abuse disorders 18,49,[67][68][69][70][71] and could explain why incubation with DHEA reduces opioid intake. Furthermore, previous reports describe a link between DHEAS and the development of opioid tolerance without showing an effect on self-administration 72 .…”

Section: Discussionmentioning

confidence: 99%

“…To screen for novel modulators of opioid self-administration, we utilized our newly developed assay to condition fish with the opioid hydrocodone. As previously described, small groups of adult zebrafish are conditioned to swim across an active platform to receive a dose of the drug 18 .…”

Section: Validation Of the Screening Methodsmentioning

confidence: 99%

“…Using a recently described paradigm to condition adult fish to self-administer the opioid hydrocodone 18 , we designed a behavior-based screen to identify novel compounds affecting opioid self-administration in zebrafish. We screened 110 unique molecules selected for their annotated activity against processes and pathways known to be involved in substance abuse disorders.…”

Section: Introductionmentioning

confidence: 99%

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The 5α-reductase inhibitor finasteride reduces opioid self-administration

Bossé

Cadeddu

Floris

et al. 2020

Preprint

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Opioid use disorder (OUD) has become a leading cause of death in the US, yet current therapeutic strategies remain highly inadequate. To identify novel potential treatments for OUD, we screened a targeted selection of over 100 drugs, using a recently developed opioid self-administration assay in zebrafish. This paradigm showed that finasteride, a steroidogenesis inhibitor approved for the treatment of benign prostatic hyperplasia and androgenetic alopecia, reduced self-administration of multiple opioids without affecting locomotion or feeding behavior. These findings were confirmed in rats; furthermore, finasteride did not interfere with the antinociceptive effect of opioids in rat models of neuropathic pain. Steroidomic analyses of the brains of fish treated with finasteride revealed a significant increase in dehydroepiandrosterone sulfate (DHEAS). Treatment with precursors of DHEAS reduced opioid self-administration in zebrafish, in a fashion akin to the effects of finasteride. Our results highlight the importance of steroidogenic pathways as a rich source of therapeutic targets for OUD and point to the potential of finasteride as a new option for this disorder.

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“…The introduction of alternative reinforcers, particularly social reinforcement, also brings these models closer to the human condition. An opioid self-administration assay in zebrafish was recently validated and provides a new translational tool for discovering the genetic and molecular bases of addiction and for screening small molecules for therapy (11).…”

mentioning

confidence: 99%