Article Figures & Data
Figures
- Figure 1.
Generation of F1, F2, and F3 mice from the PNE dams. Dams in the founder (F0) generation were exposed to nicotine in drinking water beginning 3 weeks before they were crossed with a drug-naive sire. The nicotine exposure continued throughout pregnancy. At ∼6–8 weeks of age, male and female offspring (F1) born to the PNE dams were crossed with drug-naive male and female mice, respectively, to produce the F2 generations. At ∼6–8 weeks of age, PNE-F2 female mice were crossed with drug-naive males to produce the PNE-female-derived F3 generation. PNE-F2 male mice were not used for further breeding. From each generation, 6- to 8-week-old mice were used for experimental analysis. An identical breeding plan was used to generate F1, F2, and F3 mice from the prenatally saccharin-exposed dams (data not shown).
- Figure 2.
Transgenerational transmission of hyperactivity induced by PNE. Spontaneous locomotor activity was analyzed between 17:00 and 09:00 h in the F2 (A, B) and F3 (C, D) generations. The founder mice for each generation were females from the PNE or SAC group and drug-naive males. Hourly (A, C) and cumulative (B, D) locomotor activity measurements are shown (mean ± SEM values). The cumulative activity represents locomotor activity during the lights-off period (19:00–07:00 h). Hourly measurements showed that both PNE male and female F2 (A) and F3 (C) mice showed significantly higher activity compared with the prenatal SAC counterparts. Cumulative activity showed significant effects of prenatal treatment in F2 (F(3,44) = 19.7; p = 0.0001) and F3 generations (F(3,44) = 14.3; p = 0.0001). Tukey–Kramer multiple-comparison tests showed significantly higher cumulative activity in both male and female PNE F2 and F3 mice compared with their SAC counterparts (p < 0.001). There was no significant difference between male and female mice in either the prenatal treatment group or either generation (p > 0.05). n = 12–13 for each group. PNE-induced hyperactivity is not transmitted from one generation to the next via male founders (E–F). Spontaneous locomotor activity was analyzed from 17:00–09:00 h in male F2 mice produced by breeding male PNE or SAC mice with drug-naive females. The cumulative activity represents locomotor activity during the lights-off period (19:00–07:00 h). Hourly (E) and cumulative (F) locomotor activity measurements are shown (mean ± SEM values). Hourly activity was similar between the PNE and SAC groups (E). Cumulative activity did not show significant differences between the two groups (t test, p = 0.13, n = 9 per group).
- Figure 3.
Effects of a single oral dose (0.75 mg/kg) of MPH on PNE induced spontaneous locomotor activity in male and female F2 mice derived from female founders. Locomotor activity was assayed from 17:00–09:00 h (A–D). MPH or saline (SAL) was gavaged at 19:00 h. Cumulative activity in the PNE (E) and SAC (F) groups was analyzed for the 12 h lights-off period from 19:00–07:00 h. Data are shown as means ± SEM. Hourly measurements showed that both male (A) and female (B) mice derived from PNE founders showed lower activity upon MPH administration compared with SAL administration. In the SAC group, MPH administration did not produce significant effects on the hourly activity compared with SAL administration in male (C) or female (D) mice. Cumulative activity over the entire 12 h lights-off period showed significant decreases in the PNE male and female mice (E) receiving MPH compared with SAL, whereas MPH had no significant effect on male or female mice in the SAC group (F). Cumulative activity showed significant effects of drug treatment in the PNE group (ANOVA: F(3,28) = 6.3; p = 0.003). Tukey–Kramer multiple-comparison test revealed significant differences in cumulative activity between SAL and MPH treatments for male and female mice (p < 0.05). ANOVA did not reveal significant changes in cumulative activity in the SAC group (F(3,37) = 1.02, p = 0.39).
- Figure 4.
Effects of a single oral dose (0.75 mg/kg) of MPH on PNE induced spontaneous locomotor activity in male and female F3 mice derived from female F2 founders. Locomotor activity was assayed from 17:00–09:00 h (A, B). MPH or saline (SAL) was gavaged at 19:00 h. Cumulative activity (C) was analyzed for the 12 h lights-off period from 19:00 to 07:00 h. Data are shown as mean ± SEM values. Hourly measurements showed that both male (A) and female (B) F3 mice showed lower activity upon MPH administration compared with SAL administration. Cumulative activity over the 12 h lights-off period showed significant decreases in the PNE male and female mice (C) receiving MPH compared with SAL. Statistical analysis (t test) showed significant decreases in cumulative activity in male and female mice administered MPH compared with their counterparts receiving SAL (male: t = 3.39, p = 0.04; female: t = 6.09, p = 0.01; n = 4 per group).
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