, Volume 201, Issue 1, pp 97–106

Reference-dose place conditioning with ethanol in mice: empirical and theoretical analysis

  • Peter A. Groblewski
  • Laura S. Bax
  • Christopher L. Cunningham
Original Investigation



A frequently expressed criticism of the conditioned place preference (CPP) procedure is that it sometimes lacks a graded dose–response curve for many drugs.


We used a combination of standard and reference-dose CPP procedures to examine the dose–response curve for ethanol-induced CPP in DBA/2J mice.

Materials and methods

In the standard procedure, ethanol (0.5, 1.5, 2, and 4 g/kg) was paired with a distinctive floor cue, whereas saline was paired with a different floor cue. In the reference-dose procedure, each cue was paired with a different dose of ethanol. All mice received four 5-min trials of each type in both procedures.


Standard procedures yielded similar levels of CPP at doses of 1.5, 2, and 4 g/kg, whereas 0.5 g/kg did not produce significant CPP. However, in the reference-dose procedure, exposure to the 0.5-g/kg dose interfered with CPP normally produced by 1.5 or 2 g/kg. Moreover, mice showed significant preference for the 4-g/kg-paired cue over the 1.5-g/kg-paired cue.


These studies show that a reference-dose procedure can reveal effects of low doses that are sometimes difficult to detect in a standard procedure. The reference-dose procedure may also uncover differences between higher doses that normally produce similar preference. Efficacy of the reference-dose procedure may be explained by a theoretical analysis that assumes the procedure places behavior between the extremes of the performance range, offering a more sensitive method for detecting effects of manipulations that produce small changes and/or differences in the rewarding effects of ethanol.


Conditioned place preference Reference-dose procedure Reward Ethanol Locomotor activity Inbred mice (DBA/2J) 


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Peter A. Groblewski
    • 1
    • 2
  • Laura S. Bax
    • 1
    • 2
  • Christopher L. Cunningham
    • 1
    • 2
  1. 1.Department of Behavioral Neuroscience, L470Oregon Health & Science UniversityPortlandUSA
  2. 2.Portland Alcohol Research CenterOregon Health & Science UniversityPortlandUSA

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