Fig. 5: Transcriptional consequences of social OT conditioning in Oprm1 null mice and their wild-type controls.

a In this experiment, OT administration was paired with social encounter for all the mice (“social” paradigm; 4 males – 4 females per genotype and treatment). After a pre-conditioning social interaction session, mice received per nasal OT (0.3 IU) or vehicle administration paired with the presentation of an unfamiliar mouse every two/three days over 2 weeks (D4 to D15). The mice performed a post-conditioning social interaction session on D18 and were sacrificed 45 min after the beginning of behavioural assessment for qRT-PCR analysis. b As observed in the previous experiment, OT exposure had opposite effects on social interaction in Oprm1^+/+ and Oprm1^-/- mice, inducing a severe deficit in the former while rescuing interaction in the latter (mean duration of nose contacts: H_3,32 = 23.3, p < 0.0001; mean duration of paw contacts: H_3,32 = 26.8, p < 0.0001; grooming after social contact: H_3,32 = 25.6, p < 0.0001) (more parameters in Fig. S5). c A hierarchical clustering analysis of qRT-PCR data was performed for each brain region of interest. The most contrasted transcriptional profiles were observed between OT-treated Oprm1^+/+ and OT-treated Oprm1^-/- mice in the NAc, VP/Tu, LS, and CeA, but not in the CPu and MeA where OT exposure led to more similar profiles between Oprm1^+/+ and Oprm1^-/- mice. The main transcriptional effect of OT was to down-regulate gene expression across brain regions (gene names highlighted in green), as seen in the CPu, NAc, VP/Tu, MeA and CeA, but not in the LS. d OT treatment decreased the expression of genes coding for oxytocin and vasopressin receptors (Oxtr, Avpr1a, Avpr1b) in the CPu, VP/Tu and MeA, more significantly in Oprm1^-/- than in Oprm1^+/+ mice. Similarly, OT exposure led a down-regulation of the expression of the main marker genes of SPNs, the genes coding for the dopamine D1 (Drd1a) and D2 (Drd2) receptors, and the gene coding for the adenosine 2a (Adora2) receptor. Such down-regulation was more pronounced in the VP/Tu of the Oprm1^-/- mice. Gene expression data are expressed as fold change versus Oprm1^+/+ - vehicle group (clustering or scatter plots and mean ± SEM). Comparison to Oprm1^+/+ - vehicle group (two-tailed t-test): one star p < 0.05, two stars p < 0.01, three stars p < 0.001. Letters: significant difference with vehicle-treated Oprm1^-/- group (2-tailed t-test); (c): p < 0.05, (b): p < 0.01, (a): p < 0.001. qRT-PCR data used for clustering are displayed in Table S2. More individual transcriptional profiles for candidate genes are displayed in Fig. S5.