Effect of sex and HD mutation on saccharin-preference test and total fluid intake.

<p>(A) We found a significant interaction between sex and genotype (F_(1,44) = 5.84, p<0.05) on saccharin preference (expressed as % of total fluid intake). Indeed compared to WT animals, only HD female mice exhibited reduced saccharin preference. (B) Interestingly looking at total fluid intake (expressed in mL), we revealed an overall effect of genotype (F_(1,44) = 12.3, p<0.01) but no significant effect of sex or interactions. Values represent means (± SEM) of n = 8–14 mice per group. WT vs. HD: (*) p<0.05, (**) p<0.01.</p

In vivo assessment of 5-HT_1A and 5-HT₂ post-synaptic receptor function using 8-OH-DPAT-induced change of corticosterone levels and DOI-induced head-twitches.

<p>Compared to paired-saline injected animals, administration of the 5-HT_1A agonist 8-OH-DPAT (0.3 mg/kg, s.c.) significantly increased corticosterone levels in both (A) male and (B) female mice, regardless of the genotype. In the DOI-induced head-twitches experiment (bottom panel), there was a significant effect of genotype in both sexes. Indeed, the number of head-twitches following DOI (1 mg/kg) were decreased in (C) HD male and (D) HD female mice when compared to WT animals. Values represent means (± SEM) of n = 5–10 mice per group. Saline vs. DPAT0.3: (+) p<0.05, (++) p<0.01, (+++) p<0.001 WT vs. HD: (*) p<0.05, (**) p<0.01, (***) p<0.001.</p

Concentrations of 5-HT and 5-HIAA in brain tissue.

<p>Using the HPLC system, we measured the tissue levels of serotonin (5-HT) and its metabolite 5-hydroxyindolacetic acid (5-HIAA) in several brain areas. Both 5-HT and 5-HIAA concentrations were decreased in the hippocampus (A/B), the cortex (C/D) and the striatum (E/F) in female HD mice when compared to WT animals. Levels of 5-HIAA were also reduced in male HD. Finally, male mice exhibited higher hippocampal tissue levels of both 5-HT and 5-HIAA when compared to female animals. 5-HT and 5-HIAA are expressed in ng/g tissue. Values represent means (± SEM) of n = 6–8 mice per group. WT vs. HD: (*) p<0.05, (**) p<0.01, (***) p<0.001. Male vs. female: (##) p<0.01.</p

Effect of sex and HD mutation on the novelty suppressed feeding test (NSFT).

<p>(A) Analyzing the time (expressed in sec) to complete the task in the NSFT, we found a significant interaction between sex and genotype (F_(1,55) = 4.2, p<0.05). Indeed compared to WT animals, only HD female mice exhibited greater delay to complete the NSFT. (B) Interestingly measuring the amount of food consumed after NSFT, we did not find any effect of genotype (F_(1,55) = 1.7, p = 0.19) or interaction with the sex (F_(1,55) = 0.39, p = 0.54). Values represent means (± SEM) of n = 12–17 mice per group. WT vs. HD: (***) p<0.001.</p

Gene expression of 5-HT transporter (5-HTT), 5-HT_1A receptor (5-HT_1AR) and tryptophan hydroxylase-2 (TPH2) in the raphe.

<p>Measuring mRNA levels of several genes encoding proteins that regulate 5-HT homeostasis, we found significant genotype-sex interactions for both mRNA levels of (A) 5-HTT and (B) TPH2 but not for (C) 5-HT_1AR gene expression. Both 5-HTT and TPH2 mRNA levels were decreased in female WT when compared to male WT. In addition, HD mutation decreased both 5-HTT and TPH2 gene expressions in male only. Finally 5-HT_1AR mRNA levels were not affected by either the sex or the genotype. Values represent means (± SEM) of n = 5–6 mice per group. WT vs. HD: (**) p<0.01. Male vs. female: (##) p<0.01.</p