Original Investigation

Psychopharmacology

, Volume 187, Issue 1, pp 13-21

First online:

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

  • Christopher M. OlsenAffiliated withDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical CenterCenter for Molecular Neuroscience, Vanderbilt University Medical Center Email author 
  • , Danny G. WinderAffiliated withDepartment of Molecular Physiology and Biophysics, Vanderbilt University Medical CenterCenter for Molecular Neuroscience, Vanderbilt University Medical CenterJohn F. Kennedy Center for Research on Human Development, Vanderbilt University Medical Center

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Abstract

Rationale

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.

Objectives

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.

Results

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.

Conclusions

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.

Keywords

Cocaine Self-administration Mouse