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The Journal of Neuroscience, November 15, 2002, 22(22):9905-9911
Conditional Rescue of Protein Kinase C  Regulates Ethanol
Preference and Hypnotic Sensitivity in Adult Mice
Doo-Sup
Choi,
Dan
Wang,
Jahan
Dadgar,
Wesley S.
Chang, and
Robert O.
Messing
Ernest Gallo Clinic and Research Center, Department of Neurology,
University of California, San Francisco, Emeryville, California 94608
Conventional gene targeting is a powerful tool to study the
influence of specific genes on behavior. However, conclusions relevant
for adult animals are limited by consequences of gene loss during
development. Mice lacking protein kinase C  (PKC) consume less
alcohol and show greater acute sensitivity to alcohol than do wild-type
mice. There are no selective inhibitors of PKC that can be
administered systemically and cross the blood-brain barrier to test
whether these phenotypes result from loss of PKC during development
or in adulthood. Here we used conditional expression of PKC in the
basal forebrain, amygdala, and cerebellum to rescue wild-type responses
to alcohol in adult PKC / mice. Subsequent
suppression of transgenic PKC restored
PKC/ behaviors. These findings establish
that PKC signaling in the adult brain regulates alcohol consumption
and sensitivity. If this extends to humans, then PKC inhibitors
might prove useful as novel therapeutics for alcoholism.
Key words:
protein kinase C; alcohol; ethanol; doxycycline; GABAA receptor; NMDA receptor
Copyright © 2002 Society for Neuroscience 0270-6474/02/22229905-07$05.00/0
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