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Damaging the PKA gene drives mice to drink
By Bijal P. Trivedi

Mice carrying a mutant version of the protein kinase A (PKA) gene voluntarily drink twice as much alcohol, and recover more quickly from its sedative effects, than normal mice. But it is not known whether the PKA gene is also responsible for alcoholic tendencies in humans, says Todd E. Thiele, of the University of Washington, in Seattle. His research was reported in the recent online issue of The Journal of Neuroscience.

In the brain, the PKA protein, made by the PKA gene, activates other proteins and regulates genes by turning them off or on. It is still not known if altering this gene specifically affects only alcohol consumption or whether it also makes mice prone to increased consumption and tolerance of other drugs.

Previous studies have found that alcohol consumption affects PKA. The Seattle researchers explored whether, and how, a damaged PKA gene, lacking the regulatory region RIIb, affects a mouse's desire to drink.

When offered solutions with alcohol concentrations ranging from six percent to twenty percent, the alcohol equivalent of a vodka-orange screwdriver, the PKA mutant mice consistently drank more than normal mice.

Thiele and his colleagues studied the sedative effects of alcohol by injecting it into PKA mutants and normal mice. The mutants recovered more quickly from their alcohol-induced slumbers. Both groups fell asleep within minutes. The mice were placed on their backs—not a comfortable position for a mouse—in a U-shaped trough while researchers monitored how long it took for the animals to awake and regain their coordination. Normal mice took 25 minutes longer than the mutants to flip over onto all four paws.

"Not much has been done with humans and PKA, so it is too early to suggest that these results have implications for human alcoholism," says Thiele. He says that the next step for his work is to find out in which region of the brain PKA is working to affect alcohol consumption.

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Thiele, T.E. et al. High ethanol consumption and low sensitivity to ethanol-induced sedation in protein kinase A-mutant mice. J Neurosci (Online) 20, RC75 (May 15, 2000).

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