Figure 3. Differential effect of nicotine in C57BL/6 (B6) and BTBR mice.

Bars represent (means±SEM) nicotine effect compared with vehicle on behavior outcomes changes from baseline in B6 (white background bars) mice and BTBR (gray background bars). P values reflect refer to comparisons of the effect of nicotine vs. vehicle on changes from baseline between the two (BTBR vs. B6) strains (strain*time*treatment interactions). The nicotine doses indicated at the bottom of the figure apply to all panels. A, compared with vehicle, four-week nicotine treatment at lower doses (50 and 100µg/ml) was associated with significantly greater increases (from baseline) on hotplate latency in BTBR than in B6 mice (A, strain*time*treatment interaction p=0.016 and p<0.001 for 50 and 100µg/ml respectively). Compared with vehicle, at 200 and 400µg/ml nicotine led to significant decreases in hotplate latency in BTBR, whereas in B6 mice, it lead to no significant changes or increases in hotplate latency (A, strain*time*treatment interaction p=0.040 and p<0.001 for 200 and 400µg/ml respectively). B, concerning cold sensitivity, nicotine was also associated with a different pattern of effect in BTBR compared with B6. Compared with vehicle, at lower doses (50 and 100µg/ml) nicotine led to significant increases in BTBR, whereas in B6 mice nicotine was associated with significant decreases in cold plate sensitivity (B, strain*time*treatment interaction p=0.006 and p<0.001 for 50 and 100µg/ml respectively). Nicotine at 400µg/ml, compared with vehicle, was associated decreases in cold plate sensitivity in BTBR but with no significant changes in B6 mice (B, p=0.001). C, in response to 250Hz stimulation, compared with vehicle, nicotine treatment at 200µg/ml was associated with slight increases in current thresholds in BTBR, whereas in B6, to slight decreases in current thresholds in significantly different patterns (p=0.008). N≥10 (male and female) mice for each nicotine dose. *indicates p<0.05, † p≤0.01, and ‡ p≤0.001.