Fig. 4: RapaLink-1 inhibits alcohol-dependent mTORC1 activation in the nucleus accumbens in the presence and absence of RapaBlock. | Nature Communications

Fig. 4: RapaLink-1 inhibits alcohol-dependent mTORC1 activation in the nucleus accumbens in the presence and absence of RapaBlock.

From: Brain-specific inhibition of mTORC1 eliminates side effects resulting from mTORC1 blockade in the periphery and reduces alcohol intake in mice

Fig. 4

a Timeline of experiment. Mice underwent 7 weeks of IA20%2BC. On week 8, mice received a systemic administration of vehicle (white), RapaLink-1 alone (1 mg/kg, purple), or a combination of RapaLink-1 (1 mg/kg, purple) and RapaBlock (40 mg/kg, pink) 3 h before the beginning the drinking period, and the NAc was removed at the end of the last 24 h drinking session. b, d Representative images depict S6 phosphorylation (pS6) (b) and 4E-BP phosphorylation (p4E-BP) (d) (top panels), total protein levels of S6 (b) and 4E-BP (d) (middle panels), and actin (bottom panels). c, e RapaLink-1 inhibits alcohol-dependent mTORC1 activation activity in the presence and absence of RapaBlock pS6 (one-way ANOVA: F3,20 = 41.58, p < 0.0001, r2 = 0.8618; vehicle vs. water p < 0.0001, vehicle vs. RapaLink-1 p < 0.0001, vehicle vs. RapaLink-1+RapaBlock p < 0.0001) and p4E-BP (one-way ANOVA: F3,20 = 186, p < 0.0001, r2 = 0.9654; vehicle vs. water p < 0.0001, vehicle vs. RapaLink-1 p < 0.0001, vehicle vs. RapaLink-1+RapaBlock p < 0.0001). Data are presented as the individual data points and mean densitometry values of the phosphorylated protein divided by the densitometry values of the total protein ± SEM and expressed as % of vehicle. Significance was determined using one-way ANOVA Tukey’s multiple comparisons test. n = 6 per condition. ***p < 0.001, ns = non-significant.

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