High ethanol consumption and low sensitivity to ethanol-induced sedation in protein kinase A-mutant mice.
Both in vitro and in vivo evidence indicate that cAMP-dependent protein kinase (PKA) mediates some of the acute and chronic cellular responses to alcohol. However, it is unclear whether PKA regulates voluntary alcohol consumption. We therefore studied alcohol consumption by mice that completely lack the regulatory IIbeta (RIIbeta) subunit of PKA as a result of targeted gene disruption. Here we report that RIIbeta knockout mice (RIIbeta-/-) showed incr eased consumption of solutions containing 6, 10, and 20% (v/v) ethanol when compared with wild-type mice (RIIbeta+/+). On the other hand, RIIbeta-/- mice showed normal consumption of solutions containing either sucrose or quinine. When compared with wild-type mice, the RIIbeta-/- mice were found to be less sensitive to the sedative effects of ethanol as measured by more rapid recovery from ethanol-induced sleep, even though plasma ethanol concentrations did not differ significantly from those of controls. Finally, both RIbeta- and catylatic subunit beta1-deficient mice showed normal voluntary consumption of ethanol, indicating that increased ethanol consumption is not a general characteristic associated with deletion of PKA subunits. These data demonstrate a role for the RIIbeta subunit of PKA in regulating voluntary consumption of alcohol and sensitivity to the intoxication effects that are produced by this drug.
Thiele
T E
TE
Department of Psychology, University of Washington, Seattle, Washington 98195, USA. thiele@u.washington.edu
Willis
B
B
Stadler
J
J
Reynolds
J G
JG
Bernstein
I L
IL
McKnight
G S
GS
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D017868:Cyclic AMP-Dependent Protein Kinases / Q000235:genetics* / Q000378:metabolism; D000431:Ethanol / Q000378:metabolism / Q000494:pharmacology*; D006993:Hypnotics and Sedatives / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D018345:Mice, Knockout; D011803:Quinine / Q000494:pharmacology; D013395:Sucrose / Q000494:pharmacology
D054757:Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit; D006993:Hypnotics and Sedatives; C517838:Prkar2b protein, mouse; D000431:Ethanol; D013395:Sucrose; D011803:Quinine; D017868:Cyclic AMP-Dependent Protein Kinases