Reference-dose place conditioning with ethanol in mice: empirical and theoretical analysis.
BACKGROUND
A frequently expressed criticism of the conditioned place preference (CPP) procedure is that it sometimes lacks a graded dose-response curve for many drugs.


OBJECTIVE
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.


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.


RESULTS
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.


CONCLUSIONS
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.
Groblewski
Peter A
PA
Department of Behavioral Neuroscience, L470, Oregon Health & Science University, Portland, OR 97239-3098, USA. groblews@ohsu.edu
Bax
Laura S
LS
Cunningham
Christopher L
CL
D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D003463:Cues; D004305:Dose-Response Relationship, Drug; D036262:Empirical Research; D000431:Ethanol / Q000494:pharmacology*; D007274:Injections, Intraperitoneal; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D012015:Reference Standards; D012965:Sodium Chloride / Q000008:administration & dosage; D013239:Stereotyped Behavior / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D002492:Central Nervous System Depressants; D000431:Ethanol; D012965:Sodium Chloride