Figure 8.

Type III Nrg1 heterozygous mice have prepulse inhibition deficits that are not seen if they have been treated with nicotine. A, PPI (mean ± SE) for wild-type (open bar; n = 13) and type III Nrg1 heterozygous (filled bar; n = 22) mice (4–8 months of age). PPI was calculated as percentage change between the responses to the startle stimuli with and without a prepulse. The PPI is presented at each prepulse intensity (2, 4, and 8 dB above the background of 70 dB, as indicated by +2, +4, +8 dB). A mixed-model, repeated-measure ANOVA indicated a statistically significant effect of prepulse intensity (F_(2,158) = 29.03; p < 0.0001) and that there was a significant difference between genotypes (F_(1,79) = 4.93; p_genotype < 0.03). B, Bar plot of PPI in wild-type and type III Nrg1 heterozygous mice (n = 6/genotype) before (baseline) and after 7 weeks of chronic nicotine treatment (nicotine; 200 μg/ml). Note that this experiment was run with a separate cohort of mice with the same prepulse and startle stimuli as used in A. Therefore, the result of the baseline PPI in both genotypes was an independent replication of A to detect the effects of chronic nicotine in both genotypes. A mixed ANOVA revealed a significant genotype by nicotine treatment effect (F_(1,10) = 5.63; p < 0.04). The effects of genotype (F_(1,10) = 2.8; p = 0.12) and nicotine (F_(1,10) = 1.54; p = 0.24) were not significant. Before, but not after nicotine, the heterozygous mice had significantly reduced PPI values (before, p < 0.05; after, p = 0.9; Student's t test with Scheffé's correction for multiple comparisons).