, Volume 187, Issue 1, pp 13–21

A method for single-session cocaine self-administration in the mouse

Original Investigation

DOI: 10.1007/s00213-006-0388-1

Cite this article as:
Olsen, C.M. & Winder, D.G. Psychopharmacology (2006) 187: 13. doi:10.1007/s00213-006-0388-1



Drug self-administration is a powerful method to measure the reinforcing effects of a drug, as well as to investigate behavioral, biochemical, and physiological effects of a drug specific to contingent delivery. With the spectrum of genetically modified mice available, there is a need for well-designed drug self-administration studies tailored for rapid completion of studies in mice.


We set out to develop a methodology in mice for obtaining high levels of cocaine self-administration during the first exposure to the drug.

Materials and methods

C57Bl/6J mice were trained to lever press for liquid reinforcer on a fixed ratio 1, then a progressive ratio (PR) schedule of reinforcement before intravenous self-administration of cocaine on a PR schedule.


Within a single 16-h session, each mouse self-administered either saline or 0.1, 0.3, 0.6, or 1.2 mg kg−1 infusion−1 of cocaine during four distinct 4-h subsessions. Mice showed a strong preference for cocaine vs saline, as demonstrated by higher breakpoints and greater preference for the active lever. Likewise, there was a dose-dependent increase in breakpoints obtained and in drug intake. Finally, animals receiving noncontingent cocaine pressed significantly less than mice self-administering the same dose of cocaine, indicating that a significant amount of active lever pressing is driven by drug-seeking and not the psychomotor-activating effects of cocaine alone.


Mice will reach high breakpoints and cocaine intake during an initial exposure to cocaine. This method is well-suited to rapidly obtain progressive ratio cocaine self-administration in mice.





Fixed ratio




Progressive ratio

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Department of Molecular Physiology and BiophysicsVanderbilt University Medical CenterNashvilleUSA
  2. 2.Center for Molecular NeuroscienceVanderbilt University Medical CenterNashvilleUSA
  3. 3.John F. Kennedy Center for Research on Human DevelopmentVanderbilt University Medical CenterNashvilleUSA