title: Protein kinase C epsilon modulates nicotine consumption and dopamine reward signals in the nucleus accumbens.
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 α(6) and β(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 PKCε regulates reward signaling through α(6)-containing nicotinic receptors and suggest that PKCε could be a target for the treatment of comorbid nicotine and alcohol addictions.
authors.affiliation: Ernest Gallo Clinic and Research Center, Department of Neurology, University of California at San Francisco, Emeryville, CA 94608, USA.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Lee
authors.forename: Robert O
authors.initials: RO
authors.lastname: Messing
mesh_terms: D000818:Animals; D003214:Conditioning, Classical / Q000502:physiology; D004298:Dopamine / Q000008:administration & dosage / Q000378:metabolism*; D015259:Dopamine Agents / Q000008:administration & dosage / Q000378:metabolism; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000378:metabolism; D015870:Gene Expression; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009538:Nicotine / Q000008:administration & dosage / Q000378:metabolism*; D009714:Nucleus Accumbens / Q000378:metabolism*; D051744:Protein Kinase C-epsilon / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000235:genetics; D012201:Reward; D012646:Self Administration; D015398:Signal Transduction; D013028:Space Perception / Q000502:physiology
chemical_list: D015259:Dopamine Agents; D005731:Ganglionic Stimulants; D012333:RNA, Messenger; D011978:Receptors, Nicotinic; C104518:nicotinic receptor alpha6; C568453:nicotinic receptor beta3, mouse; D009538:Nicotine; D051744:Protein Kinase C-epsilon; D004298:Dopamine