Fig. 5: VGLUT3T8I/T8I mice are more prone to habit formation and display an increased vulnerability to develop maladaptive eating compared to WT mice. | Nature Communications

Fig. 5: VGLUT3T8I/T8I mice are more prone to habit formation and display an increased vulnerability to develop maladaptive eating compared to WT mice.

From: The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice

Fig. 5

a, Number of sucrose pellets deliveries for VGLUT3T8I/T8I mice (purple) versus controls (black) during FR1 training (genotype, F1,22 = 0.0001, p = 0.992; time F3.064,67.41 = 54.11, p < 0.001; genotype x time F15,330 = 0.548, p = 0.912; two-way RM ANOVA and post hoc comparison with the method of contrasts). b, WT mice/valued vs WT mice/devalued **p = 0.001, two-sided paired t-test (n = 11 mice). VGLUT3T8i/T8i mice/valued vs VGLUT3T8i/T8i mice/devalued p = 0.945, two-sided paired t-test (n = 9 mice). c, Number of chocolate-flavored pellets deliveries during FR1 and FR5 training (genotype F1,25 = 0.059, p = 0.811; time F9.073,223.9 = 5.468, p < 0.001; genotype x time F123,3036 = 1.43, p = 0.002; Mixed effect model (REML)). d, Persistence to response (p = 0.113, two-sided unpaired t-test). e, Motivation (p = 0.677, unpaired t-test). f, Compulsivity (p = 0.597, two-sided unpaired t-test). Percentage of WT mice (g) and VGLUT3T8I/T8I mice (h) categorized as addicted or non-addicted (p = 0.918, Chi-squared test). i-k, Pearson correlations between individual values of addiction-like criteria and persistence to response (WT mice r2 = 0.334, p = 0.031; VGLUTT8I/T8I mice r2 = 0.2, p = 0.126) (i), motivation (WT mice r2 = 0.295, p = 0.045; VGLUTT8I/T8i mice r2 = 0.305, p = 0.051) (j) and compulsivity (WT mice r2 = 0.414, p = 0.013; VGLUTT8I/T8i mice r2 = 0.405, p = 0.011) (k). l-n, Sucrose binge-like overconsumption test (n = 10 WT mice and n = 10 mice for VGLUT3T8I/T8I mice). Daily sucrose consumption during 4 h (H0-H4) (genotype F1,18 = 0.96, p = 0.34; time F15,270 = 164.8, p < 0.001; genotype x time F15,270 = 1.432, p = 0.132, Two-way RM ANOVA) (l), First hour (H0-H1) (genotype F1,18 = 3.692, p = 0.071; time F5.587,100.6 = 119.5, p = <0.001; genotype x time F15,270 = 3.066, p < 0.001, Two-way RM ANOVA) (m) or last 3 h (H1-H4) (genotype F1,18 = 0.027, p = 0.872; time F15,270 = 42.37, p < 0.001; genotype x time F15,270 = 3.066, p < 0.001) (n) of access to sucrose solution. o-q, ABA model (n = 10 WT mice and n = 10 VGLUT3T8I/T8I mice). o, Survival curve (Log-rank (Mantel-Cox) post hoc comparison p < 0.001, Gehan-Breslow-Wilcoxon post hoc comparison p < 0.001, Kaplan-Meier test). p-q Effect of chronic donepezil (0.3 mg.kg−1) treatment on survival curves (Log-rank (Mantel-Cox) post hoc comparison p = 0.819, Gehan-Breslow-Wilcoxon post hoc comparison p = 0.83, Kaplan-Meier test) (p) or VGLUT3T8I/T8I mice (Log-rank (Mantel-Cox) post hoc comparison p = 0.006, Gehan-Breslow-Wilcoxon post hoc comparison p = 0.004, Kaplan-Meier test) (q). Data are presented as mean values ± SEM in a-f, i-n. Source data are provided as a Source Data file.

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