PUBLICATION

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

Authors
Bossé, G.D., Peterson, R.T.
ID
ZDB-PUB-170817-9
Date
2017
Source
Behavioural brain research   335: 158-166 (Journal)
Registered Authors
Peterson, Randall
Keywords
addiction, animal model, opioid, self-administration, zebrafish
MeSH Terms
  • Analgesics, Opioid/administration & dosage*
  • Animals
  • Behavior, Addictive/etiology
  • Behavior, Addictive/psychology
  • Behavior, Animal/drug effects
  • Conditioning, Classical/drug effects
  • Disease Models, Animal
  • Drug-Seeking Behavior*
  • Hydrocodone/administration & dosage
  • Opioid-Related Disorders/etiology
  • Opioid-Related Disorders/psychology
  • Receptors, Opioid, mu/metabolism
  • Self Administration
  • Zebrafish*
PubMed
28811180 Full text @ Behav. Brain Res.
Abstract
The zebrafish (Danio rerio) has become an excellent tool to study mental health disorders, due to its physiological and genetic similarity to humans, ease of genetic manipulation, and feasibility of small molecule screening. Zebrafish have been shown to exhibit characteristics of addiction to drugs of abuse in non-contingent assays, including conditioned place preference, but contingent assays have been limited to a single assay for alcohol consumption. Using inexpensive electronic, mechanical, and optical components, we developed an automated opioid self-administration assay for zebrafish, enabling us to measure drug seeking and gain insight into the underlying biological pathways. Zebrafish trained in the assay for five days exhibited robust self-administration, which was dependent on the function of the μ-opioid receptor. In addition, a progressive ratio protocol was used to test conditioned animals for motivation. Furthermore, conditioned fish continued to seek the drug despite an adverse consequence and showed signs of stress and anxiety upon withdrawal of the drug. Finally, we validated our assay by confirming that self-administration in zebrafish is dependent on several of the same molecular pathways as other animal models. Given the ease and throughput of this assay, it will enable identification of important biological pathways regulating drug seeking and could lead to the development of new therapeutic molecules to treat addiction.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
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Mapping