PKCε Regulates Nicotinic Behavior Response in Mice
Lower levels α6, β3 of nicotinic receptor subunit tied to behavior response
THURSDAY, Sept. 22 (HealthDay News) -- Mice lacking protein kinase C epsilon (PKCε) show lower nicotine consumption and decreased conditioned place preference for nicotine, according to an experimental study published in the Sept. 20 issue of the Proceedings of the National Academy of Sciences.
Anna M. Lee and Robert O. Messing, M.D., from the University of California at San Francisco in Emeryville, tested the hypothesis that PKCε regulates behavioral responses to nicotine. PKCε knockout (Prkce−/−) mice were generated and injected with 3 mg/kg of nicotine subcutaneously. Nicotine concentration was analyzed from plasma extracted from blood to assess the nicotine metabolism. Nicotine consumption was calculated as mg/kg/day by regular weighing of the mice housed with 24-hour access to a water bottle with 2 percent saccharin and a water bottle with 15 µg/mL nicotine and 2 percent saccharin for 31 days.
The investigators found that Prkce−/− mice self-administered less nicotine and showed decreased conditioned place preference for nicotine compared with wild-type mice. Lower nicotine consumption was observed in Prkce−/− mice compared with wild-type mice. No differences were observed in the plasma levels of nicotine between genotypes indicating no differences in the nicotinic pharmacokinetics. 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 released in nucleus accumbens were associated with these behaviors in Prkce−/− mice.
"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," the authors write.