Predictors of high ethanol consumption in RIIbeta knock-out mice: assessment of anxiety and ethanol-induced sedation.
BACKGROUND
Genetic and pharmacological evidence suggests that the cyclic adenosine monophosphate-dependent protein kinase A pathway modulates neurobiological responses to ethanol. Mutant mice lacking the RIIbeta subunit of protein kinase A (RIIbeta(-/-)) are resistant to ethanol-induced sedation and drink significantly more ethanol than littermate wild-type mice (RIIbeta(+/+)). We determined whether high ethanol intake by the RIIbeta(-/-) mice on alternate genetic backgrounds is reliably predicted by high basal levels of anxiety or resistance to the sedative effects of ethanol.


METHODS
Two-bottle choice procedures and a battery of behavioral tests (elevated plus maze, open-field activity, and zero maze) were used to assess voluntary ethanol consumption and basal levels of anxiety in RIIbeta(-/-) and RIIbeta(+/+) mice on either a C57BL/6J or a 129/SvEv x C57BL/6J genetic background. Additionally, ethanol-induced sedation and blood ethanol levels were determined in RIIbeta(-/-) and RIIbeta(+/+) mice after intraperitoneal injection of ethanol (3.8 g/kg).


RESULTS
RIIbeta(-/-) mice on both genetic backgrounds consumed more ethanol and had a greater preference for ethanol relative to RIIbeta(+/+) mice. However, RIIbeta(-/-) mice showed reduced basal levels of anxiety when maintained on the C57BL/6J background but showed increased anxiety when maintained on the 129/SvEv x C57BL/6J background. Consistent with prior research, RIIbeta(-/-) mice were resistant to the sedative effects of ethanol, regardless of the genetic background. Finally, RIIbeta(-/-) and RIIbeta(+/+) mice showed similar blood ethanol levels.


CONCLUSIONS
These results indicate that high ethanol consumption is associated with resistance to the sedative effects of ethanol but that basal levels of anxiety, as well as ethanol metabolism, do not reliably predict high ethanol drinking by RIIbeta(-/-) mice.
Fee
Jon R
JR
Department of Psychology, University of North Carolina, Chapel Hill, North Carolina 27599-3270, USA.
Sparta
Dennis R
DR
Knapp
Darin J
DJ
Breese
George R
GR
Picker
Mitchell J
MJ
Thiele
Todd E
TE
D000428:Alcohol Drinking / Q000235:genetics* / Q000378:metabolism*; D000818:Animals; D001007:Anxiety / Q000201:enzymology* / Q000235:genetics*; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D006993:Hypnotics and Sedatives / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011237:Predictive Value of Tests; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D012890:Sleep / Q000187:drug effects / Q000502:physiology
D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D006993:Hypnotics and Sedatives; C517838:Prkar2b protein, mouse; D000431:Ethanol; D017868:Cyclic AMP-Dependent Protein Kinases