期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 108, 期 38, 页码 16080-16085出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1106277108
关键词
-
资金
- US Public Health Service [AA013588]
- state of California for medical research on alcohol and substance abuse through the University of California at San Francisco
- Canadian Institute of Health Research
Nicotine addiction and alcohol use disorders are very widespread and often occur together. Currently, there is no single drug approved for the simultaneous treatment of both conditions. Although these conditions share common genetic factors, the molecular mechanisms underlying their comorbidity are unknown. We have previously shown that mice lacking protein kinase C epsilon (PKC epsilon) show decreased ethanol self-administration and reward as well as increased aversion to ethanol. Here we find that Prkce(-/-) mice self-administer less nicotine and show decreased conditioned place preference for nicotine compared with wild-type mice. In Prkce(-/-) mice, these behaviors are associated with reduced levels of alpha(6) and beta(3) nicotinic receptor subunit mRNA in the ventral midbrain and striatum as well as a functional deficit in cholinergic modulation of dopamine release in nucleus accumbens. Our results indicate that PKC epsilon regulates reward signaling through alpha(6)-containing nicotinic receptors and suggest that PKC epsilon could be a target for the treatment of comorbid nicotine and alcohol addictions.
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