Figure 5. Chronic treatment with nicotine and withdrawal results in differential behavioral responses in the F1 wildtype and NRG3^ska mice.

NRG3^ska mice were treated in vivo with either saline, nicotine (18 mg/kg/day), or undergoing 24h withdrawal (WD) from nicotine. F1 hybrid mice were treated in vivo with either saline, nicotine (18 mg/kg/day), or undergoing 24h withdrawal (WD) from nicotine; additionally, these mice also received daily injections of either vehicle or afatinib at the concentrations indicated for 10 days. A) NRG3^ska mice treated with saline, nicotine, or 24h WD were tested in the NIH test. Mice chronically treated with either nicotine or 24h WD displayed a reduced latency to feed on novel test day compared to saline controls (N=16). B) NRG3^ska mice treated with saline, nicotine, or 24h WD were tested in the marble-burying test. Mice chronically treated with either nicotine or 24h WD buried fewer marbles compared to saline controls (N=10). C) Locomotor activity was tested in NRG3^ska mice treated with saline, nicotine, or 24h WD. No treatment effects were observed (N=4–6). D) F1 hybrid mice treated with saline, nicotine, 24h WD, or 24h WD + Afatinib were tested in the NIH test. Mice chronically treated with either nicotine or 24h WD + Afatinib displayed a reduced latency to feed on novel test day compared to the saline group or the 24hWD group (N=6–7). E) F1 hybrid mice treated with saline, nicotine, 24h WD, or 24h WD + Afatinib were tested in the marble-burying test. Mice chronically treated with either nicotine or 24h WD + 20mg/kg Afatinib buried fewer marbles compared to saline controls (N=5–7). F) Locomotor activity was tested in treated F1 Hybrid mice. No treatment effects were observed (N=4–6). Significant compared to vehicle control - **, p<0.01; ***, p<0.005. Significant compared to 24hWD - #, p<0.05; ###, p<0.005.