Fig. 2: Nicotine in adolescence, but not in adulthood, reshapes brain-wide responsiveness to acute nicotine. | Nature Communications

Fig. 2: Nicotine in adolescence, but not in adulthood, reshapes brain-wide responsiveness to acute nicotine.

From: Transient nicotine exposure in early adolescent male mice freezes their dopamine circuits in an immature state

Fig. 2

A Experimental timeline for mice treated with Nicotine (NIC; 100 μg/mL nicotine in 2% saccharin) or Saccharin (SAC; 2% saccharin only) in early adolescence or in adulthood. A’ iDISCO brain clearing and Clearmap activity mapping pipeline. B (Left) Mice treated with NIC in adolescence show greater cFos activity across the brain, and in specific brain regions, following an acute nicotine injection when compared to their SAC-treated counterparts. Overall, 129 regions showed an increase in cFos activity in NIC-pretreated mice, defined as a fold change >0 and a log p > 1.3 (equivalent to p < 0.05). Notable regions of interest associated with anxiety response and/or response to nicotine have been highlighted. (Right) The activation profile of mice treated with NIC in adulthood is not substantially different from their SAC-treated counterparts. Cell counts were compared with independent two-sample Student’s t tests assuming unequal variances, and p-values were converted to q-values to control for false discovery rate. C Correlation matrices of relationships between cFos cell numbers in response to nicotine injection. Activation across brain regions in SAC-pretreated mice (left) is highly correlated, and hierarchical clustering organizes these regions into 4 distinct modules with the strongest inter-region relationships. In NIC-pretreated mice (right), correlations between regions are less strong. Bottom, community analysis on networks formed from these correlation matrices indicate significant reorganization of the VTA-NAc-AMG connections. D Voxel-by-voxel analysis of these regions reveals increases in nicotine reactivity within the VTA and DA terminal regions. P-Value maps of significant differences between groups were generated from comparisons by independent two-sample Student’s t tests assuming unequal variances. Green or red voxels indicate a p <0.05 after FDR correction. All statistical comparisons were two-sided. Source data are provided as a Source Data file.

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