Nicotine Exposure during Adolescence Leads to Changes of Synaptic Plasticity and Intrinsic Excitability of Mice Insular Pyramidal Cells at Later Life

To find satisfactory treatment for nicotine addiction, synaptic and cellular mechanisms should be investigated comprehensively. Synaptic transmission, plasticity and intrinsic excitability in various brain regions are known to be altered by acute nicotine exposure. However, it has not been addressed whether and how nicotine exposure during adolescence alters these synaptic events and intrinsic excitability in the insular cortex in adulthood. To address this question, we performed whole-cell patch-clamp recordings to examine the effects of adolescent nicotine exposure on synaptic transmission, plasticity and intrinsic excitability in layer V pyramidal neurons (PNs) of the mice insular cortex five weeks after the treatment. We found that excitatory synaptic transmission and potentiation were enhanced in these neurons. Following adolescent nicotine exposure, insular layer V PNs displayed enhanced intrinsic excitability, which was reflected in changes in relationship between current strength and spike number, inter-spike interval, spike current threshold and refractory period. In addition, spike-timing precision evaluated by standard deviation of spike timing was decreased following nicotine exposure. Our data indicate that adolescent nicotine exposure enhances synaptic transmission, plasticity and intrinsic excitability in layer V PNs of the mice insular cortex at later life, which might contribute to severe nicotine dependence in adulthood.

Part Three: Biomarker Changes in Cigarette Smokers Switched to Vuse Solo or Abstinence: A Randomized, Controlled Study

Biomarkers of exposure (BoE) can help evaluate exposure to combustion-related, tobacco-specific toxicants after smokers switch from cigarettes to potentially less-harmful products like electronic nicotine delivery systems (ENDS). This paper reports data for one (Vuse Solo Original) of three products evaluated in a randomized, controlled confinement study of BoE in smokers switched to ENDS. Subjects smoked their usual brand cigarette ad libitum for two days, then were randomized to one of three ENDS for a 7-day ad libitum use period, or to smoking abstinence. Thirteen BoE were assessed at baseline and Day 5, and percent change in mean values for each BoE was calculated. Biomarkers of potential harm (BoPH) linked to oxidative stress, platelet activation, and inflammation were also assessed. Levels decreased among subjects randomized to Vuse Solo versus Abstinence, respectively, for the following BoE: 42–96% vs. 52–97% (non-nicotine constituents); 51% vs. 55% (blood carboxyhemoglobin); and 29% vs. 96% (nicotine exposure). Significant decreases were observed in three BoPH: leukotriene E4, 11-dehydro-thromboxane B2, and 2,3-dinor thromboxane B2 on Day 7 in the Vuse Solo and Abstinence groups. These findings show that ENDS use results in substantially reduced exposure to toxicants compared to smoking, which may lead to reduced biological effects.