Protein kinase C epsilon modulates nicotine consumption and dopamine reward signals in the nucleus accumbens

摘要

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 (PKCe) 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 α_6 and β_3 nicotinic receptor subunit mRNA in the ventral mid-brain and striatum as well as a functional deficit in cholinergic modulation of dopamine release in nucleus accumbens. Our results indicate that PKCe regulates reward signaling through α_6-contain-ing nicotinic receptors and suggest that PKCe could be a target for the treatment of comorbid nicotine and alcohol addictions.