Skip to main content

Zebrafish Conditioned Place Preference Models of Drug Reinforcement and Relapse to Drug Seeking

  • Protocol
  • First Online:
Zebrafish Neurobehavioral Protocols

Part of the book series: Neuromethods ((NM,volume 51))


This protocol details simple zebrafish conditioned place preference assays for assessing reinforcing properties of drugs of abuse such as ethanol, which can be administered to the tank water. We further describe a conditioned place preference assay of stimulus-induced reinstatement of drug-seeking in zebrafish. The test apparatus consists of a 1.5 L tank that can be divided into two compartments using a Perspex divider and environmental cues that can be placed around the tank. Drug exposure is paired with visual environmental cues at either end of the tank, and a change in preference towards the drug-paired end is taken as indicative of a reinforcing effect of the drug. Using the treatment paradigm described, a 30–50% ethanol-induced change in place preference is observed. Following extinction, this place preference can be reinstated by low-dose, non-contingent ethanol exposure. The simple procedures described here can be used to gain insight into genetic mechanisms contributing to vulnerability to drug dependence and addiction.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others


  1. O‘Brien, C.P. & Gardner, E.L. Critical assessment of how to study addiction and its treatment: human and non-human animal models. Pharmacol. Ther. 108, 18–58 (2005).

    Article  PubMed  Google Scholar 

  2. Lieschke, G.J. & Currie, P.D. Animal models of human disease: zebrafish swim into view. Natl. Rev. Genet. 8, 353–367 (2007).

    Article  CAS  Google Scholar 

  3. Bretaud, S., Li, Q., Lockwood, B.L., Kobayashi, K., Lin, E., & Guo, S. A choice behavior for morphine reveals experience-dependent drug preference and underlying neural substrates in developing larval zebrafish. Neuroscience 146, 1109–1116 (2007).

    Article  PubMed  CAS  Google Scholar 

  4. Darland, T. & Dowling, J.E. Behavioral screening for cocaine sensitivity in mutagenized zebrafish. Proc. Natl. Acad. Sci. U. S. A. 98, 11691–11696 (2001).

    Article  PubMed  CAS  Google Scholar 

  5. Kily, L.J., Cowe, Y.C., Hussain, O., Patel, S., McElwaine, S., Cotter, F.E., & Brennan, C.H. Gene expression changes in a zebrafish model of drug dependency suggest conservation of neuro-adaptation pathways. J. Exp. Biol. 211, 1623–1634 (2008).

    Article  PubMed  CAS  Google Scholar 

  6. Ninkovic, J., Folchert, A., Makhankov, Y.V., Neuhauss, S.C., Sillaber, I., Straehle, U., & Bally-Cuif, L. Genetic identification of AChE as a positive modulator of addiction to the psychostimulant D-amphetamine in zebrafish. J. Neurobiol. 66, 463–475 (2006).

    Article  PubMed  CAS  Google Scholar 

  7. Brennan, C.H., Parmar, A., Kily, L.K.M., Ananthathevan, A., Doshi, A., & Patel, S. Conditioned place preference models of drug-dependence and relapse to drug seeking: studies with nicotine and ethanol. Zebrafish Models Neurobehav. Res. (2010).

    Google Scholar 

  8. Wright, D. & Krause, J. Repeated measures of shoaling tendency in zebrafish (Danio rerio) and other small teleost fishes. Natl. Protoc. 1, 1828–1831 (2006).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations


Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2011 Springer Science+Business Media, LLC

About this protocol

Cite this protocol

Parmar, A., Parmar, M., Brennan, C.H. (2011). Zebrafish Conditioned Place Preference Models of Drug Reinforcement and Relapse to Drug Seeking. In: Kalueff, A., Cachat, J. (eds) Zebrafish Neurobehavioral Protocols. Neuromethods, vol 51. Humana Press.

Download citation

  • DOI:

  • Published:

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-60761-952-9

  • Online ISBN: 978-1-60761-953-6

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics