Reduced ethanol-induced conditioned taste aversion and conditioned place preference in GIRK2 null mutant mice.
BACKGROUND
Previous studies have shown that GIRK2 channel function is enhanced by ethanol and that GIRK2 null mutant mice are less sensitive to some of ethanol's effects, including anxiolysis, habituated locomotor stimulation, and acute handling-induced convulsions than wild types. Under some conditions, GIRK2 knockout mice consume more ethanol than wild types, but it is unclear whether they do so because they are more sensitive to ethanol's rewarding effects or less sensitive to its aversive effects.


OBJECTIVE
To further assess the role of GIRK2 in ethanol action, GIRK2 null mutant and wild type mice were tested in conditioning models that measure the motivational effects of ethanol.


METHODS
In a conditioned taste aversion (CTA) procedure, knockout and wild type mice were given ethanol (0.0, 2.0, 2.5, or 3.5 g/kg, IP) following 1-h access to saccharin every 48 h over a 10 day period. In a conditioned place preference (CPP) procedure, knockout and wild type mice were given ethanol (2.0 or 3.0 g/kg, IP) paired with one stimulus (grid or hole floor) and saline paired with the other. After four 5-min trials with each stimulus, a 60-min choice test was done.


RESULTS
The results demonstrated a genotypic difference in both paradigms. In CTA, there was no difference between genotypes at 0.0 or 3.5 g/kg ethanol, but at the 2.0 and 2.5 g/kg doses, wild types developed a stronger aversion to saccharin than knockouts. In CPP, wild types developed place preference, but knockouts did not.


CONCLUSIONS
These studies show that GIRK2 deletion reduced ethanol's impact in tasks that are commonly used to index the drug's rewarding and aversive effects. These findings could reflect either a learning/memory deficit or decreased sensitivity to ethanol's motivational effects in null mutant mice. The latter interpretation is more consistent with previous data showing that knockout mice consume higher doses of ethanol than wild type mice.
Department of Behavioral Neuroscience and Portland Alcohol Research Center, Oregon Health and Science University, Portland, OR 97201-3098, USA. hillkat@ohsu.edu
Katherine G
KG
Hill
Herminia
H
Alva
Yuri A
YA
Blednov
Christopher L
CL
Cunningham
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects*; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D005838:Genotype; D051379:Mice; D018345:Mice, Knockout; D009042:Motivation; D015221:Potassium Channels / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying; D012201:Reward; D013649:Taste / Q000187:drug effects*
D051676:G Protein-Coupled Inwardly-Rectifying Potassium Channels; D015221:Potassium Channels; D024661:Potassium Channels, Inwardly Rectifying; D000431:Ethanol