Better explicating the strengths and shortcomings of these models will help refine projections and improve transparency in the years ahead.
Image credit: Witsawat.S.
Edited by Leslie Lars Iversen, University of Oxford, Oxford, United Kingdom, and approved August 19, 2011 (received for review April 19, 2011)
Abstract
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 (PKCε) 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 α6 and β3 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 PKCε regulates reward signaling through α6-containing nicotinic receptors and suggest that PKCε could be a target for the treatment of comorbid nicotine and alcohol addictions.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: romes{at}gallo.ucsf.edu.
Author contributions: A.M.L. and R.O.M. designed research; A.M.L. performed research; A.M.L. and R.O.M. analyzed data; and A.M.L. and R.O.M. wrote the paper.
The authors declare no conflict of interest.
This article is a PNAS Direct Submission.
Protein kinase C epsilon modulates nicotine consumption and dopamine reward signals in the nucleus accumbens
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- Biological Sciences
- Neuroscience
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