(a) Schematic of experiment. Bilateral injections of either AAV5-CMV-GFP or AAV5-CMV-Cre-GFP into Htr2cflox/Y mice (left). Representative image of injection site (right). Scale bar = 200 μm. (b) Representative images validating knockout of Htr2c through in situ hybridisation. Scale bar = 40 μm. (c) Quantification of Htr2c knockout. Two-tailed Mann-Whitney test, P =0.0095. CMV-GFP N = 6 mice. CMV-Cre-GFP N =4 mice. (d) Water intake during sodium depletion: Two-Way Repeated Measures ANOVA: time (F(4,60) = 39.08, P < 0.0001), treatment (F(1, 15) = 2.092, P = 0.1686), interaction (F(4, 60) = 1.389, P = 0.2485). 300 mM NaCl intake during sodium depletion: Two-Way Repeated Measures ANOVA: time (F(4,60) = 101.3, P < 0.0001), treatment (F(1, 15) = 4.521, P = 0.0505), interaction (F(4, 60) = 4.141, P = 0.005). CMV-GFP N = 9 mice, CMV-Cre-GFP N = 8 mice. (e) Water intake during dehydration: Two-Way Repeated Measures ANOVA: time (F(4,60) = 140.1, P < 0.0001), treatment (F(1, 15) = 1.249, P = 0.2813), interaction (F(4, 60) = 1.024, P = 0.4021). 300 mM NaCl intake during dehydration: Two-Way Repeated Measures ANOVA: time (F(4,60) = 48.04, P < 0.0001), treatment (F(1, 15) = 5.117, P = 0.039), interaction (F(4, 60) = 4.276, P = 0.0041). CMV-GFP N = 9 mice, CMV-Cre-GFP N = 8 mice. (f) Control diet food intake (left): Two-Way Repeated Measures ANOVA: time (F(3, 45) = 302.9, P < 0.0001), treatment (F(1, 15) = 1.976, P = 0.1802), interaction (F(3, 45) = 1.405, P = 0.2538). Sodium-deficient diet food intake (right): Two-Way Repeated Measures ANOVA: time (F(3,45) = 465.2, P < 0.0001), treatment (F(1, 15) = 0.1966, P = 0.6638), interaction (F(3, 45) = 0.5274, P = 0.6657). CMV-GFP N = 9 mice, CMV-Cre-GFP N = 8 mice. (g) Water intake during euvolemia: Two-Way Repeated Measures ANOVA: time (F(4,24) = 36.98, P < 0.0001), treatment (F(1, 6) = 1.254, P = 0.3056), interaction (F(4, 24) = 0.573, P = 0.6848). 300 mM NaCl intake during euvolemia: Two-Way Repeated Measures ANOVA: time (F(4,24) = 25.79, P < 0.0001), treatment (F(1, 6) = 0.9208, P = 0.3743), interaction (F(4, 24) = 0.5215, P = 0.7208). CMV-GFP N = 4 mice, CMV-Cre-GFP N = 4 mice. All post hoc tests done using the Bonferroni correction. All data represented as mean ± s.e.m. *P < 0.05, **P < 0.01.