Fig. 1.

Effect of chronic nicotine on WT mice. (A) Semiquantitative analysis indicates that [¹²⁵I]-epibatidine binding increases under chronic nicotine treatment in regions such as LatSep, NuAc, CPu, Mot., Pr+Il., Cing., and Pr. SS. Results are expressed in arbitrary units (mean ± SEM, n = 4–6 animals per group; two samples Wilcoxon test, ∗, P < 0.05; ∗∗, P < 0.01). LatSep, lateral septum; NuAc, nucleus accumbens; CPu, caudate putamen; Pr. SS, primary somatosensory cortex; Pr+Il, prelimbic and infralimbic cortex; Cing, cingulate cortex; Mot., motor cortex. (B) Effect of chronic nicotine on WT mice behavior. (Upper) Open-field experimental analysis. Four parameters quantifying exploratory behaviors in open-field were used (see Methods). The index of exploration defined as the ratio of the time spent in exploration divided by time spent in navigation. %PA-CA, the conditional probability of transition from state PA to state. %CA-CI, the conditional probability of transition from state CA to state CI. (#PA-CA-PA, the total number of large movements across the center of the open-field sequences. (Lower) Comparison of parameters quantifying exploratory behaviors in saline condition (n = 29) and under nicotine exposure (n = 34). These parameters are normalized by values obtained in WT animal under saline condition (=100%, horizontal dashed line). Detailed analyses of behavior indicate no effect of nicotine on the time spent in navigation over the time spent in exploration (Explo index), % PA-CA, % CA-CI, or #PA-CA-PA. Two samples Student's t test, df = 61; P = 0.62, 1, 0.24, and 0.12, respectively. (C) Effect of chronic nicotine on VTA DA neuron firing pattern of WT mice. (Left) Sample raw traces of DA neuron firing patterns. (Right) Firing pattern analysis after Sal (WT sal, n = 28) or Nic exposure (WT nic, n = 33). Barplot of mean frequency of VTA DA neurons (two samples Student's t test, df = 59; P = 0.55). Cumulative distribution of percentage of burst firing (Wilcoxon test; P = 0.62).