Fig. 2: Alcohol via mTORC1 represses the translation of Aldolase A, PPM1E and Rbfox2 in the NAc.

Mice underwent 7 weeks of IA20%-2BC (Supplementary Table 1) and were treated with 20 mg/kg rapamycin as described above. A–C Polysomal mRNA levels of Aldolase A (A), PPM1E (B) and Rbfox2 (C). Each data point represents an average of 3 technical replicates. Data are presented as the average ratio of each transcript to GAPDH ± SEM and expressed as the % of water+vehicle. ***p < 0.001. n = 5 mice per group. Significance was determined using Two-way ANOVA followed by Tukey’s multiple comparisons test. A Alcohol x Rapamycin: F(1, 16) = 18.01, p = 0.0006, effect of Alcohol: F(1, 16) = 16.38, p = 0.0009, Effect of Rapamycin: F(1, 16) = 15.56, p = 0.0012; water and alcohol within the vehicle group, p = 0.0001, vehicle and rapamycin within the alcohol group, p = 0.0001. B Alcohol x Rapamycin: F(1, 16) = 12.86, p = 0.0025, effect of Alcohol: F(1, 16) = 10.51, p = 0.0051, Effect of Rapamycin: F(1, 16) = 19.13, p = 0.0005; water and alcohol within the vehicle group, p = 0.001, vehicle and rapamycin within the alcohol group, p = 0.0002. C Alcohol x Rapamycin: F(1, 16) = 27.39, p < 0.0001, effect of Alcohol: F(1, 16) = 18.9, p = 0.0005, Effect of Rapamycin: F(1, 16) = 11, p = 0.0044; water and alcohol within the vehicle group, p < 0.0001, vehicle and rapamycin within the alcohol group, p < 0.0001. D–I Aldolase A (D, G), PPM1E (E, H) and Rbfox2 (F, I) protein levels were determined by western blot analysis. Data are presented as the average ratio of Aldolase A, PPM1E and Rbfox2 to Tubulin±SEM and are expressed as the % of water control. *p < 0.05, ***p < 0.001. n = 8 mice per group. Significance was determined using two-tailed unpaired t-tests. G t(14) = 4.413, p = 0.0006; H t(14) = 5.426, p < 0.0001; I t(14) = 2.917, p = 0.0113. J Alcohol activates mTORC1 signaling in the NAc which in turn decreases the translation of Aldolase A, Rbfox2, PPM1E. Source data are provided as a Source Data file.