Fig. 6: Concomitant activation of D1- and inhibition of D2-neurons precipitates weight loss in rodent models of anorexia nervosa.

A, B Measures of weight variation (A; Two-way RM ANOVA; Virus effect F(2, 27) = 4.600, p = 0.0191; Interaction F(12, 162) = 10.63, p = 0.0001; Post-hoc WT vs D1Gq-D2Gi: 1.5 g (Day 5) p = 0.0467, 1.5 g (Day 6) p = 0.0212) and wheel-running (B; Two-way RM ANOVA; Virus effect F(2, 23) = 7.484, p = 0.0031; Interaction F(12, 136) = 5.156, p = 0.0001; Post-hoc WT vs D1Gq-D2Gi: 3 g p = 0.0027, 2.5 g p = 0.0085, 2 g p = 0.0429, 1.5 g (Day 5) p = 0.0318, 1.5 g (Day 7) p = 0.0648) in a procedure of progressive food restriction. C Dosage of plasma leptin and ghrelin levels and weight following the food-restriction procedure (One way ANOVA; Leptin F(2.00, 15.65) = 10.99, p = 0.0010; Post-hoc WT vs D1Gq-D2Gi p = 0.0038; Post-hoc WT vs D1Gi-D2Gq p = 0.1179; Post-hoc D1Gq-D2Gi vs D1Gi-D2Gq p = 0.0088; Ghrelin F(2, 22) = 4.870, p = 0.0177; Post-hoc WT vs D1Gi-D2Gq p = 0.0142; Weight F(2, 29) = 7.048, p = 0.0032; Post-hoc WT vs D1Gi-D2Gq p = 0.0029; Post-hoc D1Gq-D2Gi vs D1Gi-D2Gq p = 0.0463. D–G Measures of weight variation (D; Two-way RM ANOVA; group effect F(2, 22) = 17.45, p = 0.0001; Interaction F(10, 105) = 7.702, p = 0.0001; Post-hoc D1-D2WT vs D1Gq-D2Gi: D2 p = 0.0046, D3 p = 0.0312, D5 p = 0.0220; Post-hoc D1-D2WT vs D1GI-D2Gq: D2 p = 0.0051, D3 p = 0.0038, D4 p = 0.0006, D5 p = 0.0001), wheel running (E; Two-way RM ANOVA; group effect F(2, 22) = 7.078, p = 0.0042; Interaction F(22, 232) = 9.935, p = 0.0001; Post-hoc D1-D2WT vs D1Gq-D2Gi: Night 1 p = 0.0004, Night 2 p = 0.0051; Post-hoc D1-D2WT vs D1GI-D2Gq: Night 1 p = 0.0023, Night 2 p = 0.0001, Night 3 p = 0.0001, Night 4 p = 0.0190, Night 5 p = 0.0381) and chow consumption (F) in an Activity-Based Anorexia (ABA) model. G Probability of survival (i.e. % of animals displaying less than 20% weight loss) over the ABA procedure (Log rank test: D1Gi-D2Gq vs D1Gq-D2Gi χ2 = 5.583, p = 0.0189). Food restriction and dosage: D1-D2 WT n = 9, D1Gi-D2Gq n = 9, D1Gq-D2Gi n = 8; ABA: D1-D2 WT n = 8, D1Gi-D2Gq n = 9, D1Gq-D2Gi n = 8. $: 0.05 < p < 0.1 *: p < 0.05; **: p < 0.01; ***: p < 0.001 Error bars = s.e.m. Detailed statistics are displayed in Supplementary Table 2. Source data are provided as a Source Data file.