Fig. 1: Brief exposure to nicotine in adolescence induces a life-long imbalance between the rewarding and anxiogenic effects of later exposure.

A Top: Experimental timeline. Bottom: Timeline for the oral free-choice self-administration paradigm. B Adult mice exposed to NIC in adolescence (left) show equivalent preference for a sucrose solution as their SAC-treated counterparts. Adult mice exposed to NIC in adolescence showed a higher percentage intake of the nicotine-containing solution over all treatment doses (center). NIC-pretreated mice self-administered a higher daily dose of nicotine, with a significant difference at the 100 μg/ml dose (right, Table 1A−C). C Adult mice exposed to NIC in adulthood (left) show equivalent preference for a sucrose solution as their SAC-treated counterparts. Mice pretreated with NIC in adulthood also did not differ from controls in the percentage of nicotine solution consumed (center), nor by their daily dose of nicotine (right, Table 1D−F). D Experimental timeline. E The anxiogenic properties of an acute nicotine injection are maintained in mice pretreated with SAC in adolescence (left) but blocked in adult mice that were treated with NIC in adolescence (right, Table 1G). Graphs are separated by pre-treatment group for clarity, all statistical analyses were conducted on all four treatment conditions. F Adult mice treated with SAC in adolescence did not show CPP to a 0.2 mg/kg dose of nicotine. Adult mice treated with NIC in adolescence, however, showed CPP to this low dose of nicotine (Table 1H). G Experimental timeline. H Mice treated with NIC in adulthood show an equivalent anxiety-like response to acute nicotine (right) as their SAC-treated counterparts (left, Table 1I). Graphs are separated by pre-treatment group for clarity, but statistical analyses compared all four treatment conditions. I Mice treated with NIC or SAC as adults do not show CPP to a low dose of nicotine (Table 1J). All line graphs are presented as mean values ± SEM. Heatmaps are from representative individual animals. ^†p < 0.08, *p < 0.05, **p < 0.01, ***p < 0.01, ns = not significant. All statistical comparisons were two-sided. Holm’s sequential Bonferroni corrections were used to correct for multiple comparisons. Detailed information about statistical testing is available in Table 1. Source data are provided as a Source Data file.