Fig. 3
Oxytocin modulates socially transmitted fear behavior and neural mechanisms. a Schematic of oxytocin drug regimens and times of sample collection for qRT-PCR and immunohistochemistry (IHC; habit, habituation; cond, demonstrator conditioning; OXT, oxytocin; OXTA, oxytocin receptor antagonist). b In behaviorally naïve mice administered acute intranasal oxytocin (20 μg/kg; dark blue, n = 10), concentrations of the neuropeptide in CSF were significantly elevated compared to saline-treated controls (gray, n = 10) (two-tailed Student’s t-test: t(19) = 2.73, p = 0.015). c Unfamiliar male observers given acute (20 μg/kg, single dose, 30 min prior; dark blue, n = 12; two-tailed Student’s t-test: t(23) = 2.49, p = 0.020) or chronic (20 μg/kg, 5 daily doses; light blue, n = 11; two-tailed Student’s t-test: t(21) = 2.64, p = 0.016) intranasal oxytocin exhibited a significant enhancement of freezing compared to saline-treated controls (gray, n = 12/11, respectively). White lines and gray boxes within bars indicate mean and s.e.m. of freezing counts, respectively, during acclimation. d Immunofluorescent labeling of c-Fos+ and DAPI cells within the anterior cingulate cortex (Cg1/2) and primary motor area (M1) (scale bar, 100 μm). Acute intranasal oxytocin significantly enhanced the percentage of c-Fos+/DAPI cells within the ACC (two-tailed Student’s t-test: t(9) = 2.36, p = 0.048) but not M1 (two-tailed Student’s t-test: t(9) = 0.96, p = 0.369) (n = 5 mice per group). e Chronic intranasal oxytocin significantly reduced oxytocin receptor (Oxtr) transcript expression in the lateral division of the central nucleus of the amygdala (CeL) (two-tailed Student’s t-test: t(19) = 2.08, p = 0.05), but not the ACC (two-tailed Student’s t-test, t(19) = 0.06, p = 0.95), assayed one day after completion of chronic oxytocin treatment. qRT-PCR amplicons of the Gapdh (110 bps) and Oxtr (135 bps) transcripts at expected sizes. f Familiar male observers systemically administered the oxytocin receptor antagonist L-368,899 hydrochloride (OXTA; I.P. single dose, 30 min prior; red, n = 12 per group) showed dose-dependent reductions in socially transmitted fear at 5 mg/kg and 10 mg/kg, compared to saline-treated controls (ANOVA: F 2,35 = 5.73, p = 0.007). Error bars represent s.e.m. *p < 0.05; **p < 0.01
