Peripheral oxytocin administration buffers autonomic but not behavioral responses to environmental stressors in isolated prairie voles

Figures & data

Table I.  Timeline of procedures in this study.

Day(s)	Time periods (h)	Activity
1	0800–1600	Implantation of radiotelemetry transmitters under anesthesia
2–5	0000–2400	Recovery in divided cages, continuous
6–15	0000–2400	Recovery in home cages (with sibling), continuous
16–44	0000–2400	Pairing or isolation, continuous
30–44	0900–1100	Vehicle (50 μl, sc) or oxytocin (20 μg/50 μl, sc) injections, once daily
46	0900–1330	EPM, 5 min
48	0900–1330	RI test, 5 min
50	0900–1330	Euthanize under anesthesia and collection of brain tissue

Table II.  Behavioral responses in the open and closed arms of the 5-min EPM test in prairie voles following 4 weeks of social isolation or pairing plus daily exogenous administration of either oxytocin (20 μg/50 μl/vole, sc) or sterile saline vehicle (50 μl/vole, sc).

	Open arm duration (s)	Closed arm duration (s)	Activity (cpm)
Paired+V (n = 6)	46.9 ± 16.7	190.4 ± 21.4	27.8 ± 6.7
Paired+OT (n = 6)	50.3 ± 6.0	192.7 ± 33.0	24.9 ± 11.1
Isolated+V (n = 7)	12.1 ± 5.0*	207.0 ± 16.3*	29.7 ± 8.6
Isolated+OT (n = 5)	11.6 ± 8.1*	262.2 ± 13.3*	30.0 ± 14.2

Note: Values represent mean ± SEM. Two-way independent-groups ANOVA with Bonferroni-corrected t-tests for multiple comparisons: ^*P < 0.05 versus respective paired groups. Abbreviations: ANOVA, analyses of variance; cpm, counts per minute; OT, oxytocin; SEM, standard error of the mean; V, vehicle.

Figure 1.  Mean ( + SEM) HR (Panel A), SDNN Index (Panel B), and amplitude of RSA (Panel C) before, during, and following the 5-min EPM test in prairie voles following 4 weeks of social isolation or pairing plus daily exogenous administration of either oxytocin (20 μg/50 μl/vole, sc) or sterile saline vehicle (50 μl/vole, sc), in the following groups: Paired+V (‐‐▴‐‐; n = 6), Paired+OT (—▴—; n = 5), Isolated+V (‐‐▪‐‐; n = 6), and Isolated+OT (—▪—; n = 5). Three-factor mixed-design ANOVA with post-hoc multiple comparisons: ^*P < 0.05 versus Paired+V, Paired+OT, and Isolated+OT groups at the same time point; ^†P < 0.05 versus two paired groups at the same time point; ^‡P < 0.05 versus respective EPM value. Abbreviations: ANOVA, analyses of variance; EPM, elevated plus maze; HR, heart rate; OT, oxytocin; RSA, respiratory sinus arrhythmia; SDNN, SD of normal-to-normal intervals; SEM, standard error of the mean; V, vehicle.

Table III.  Behavioral responses in the 5-min RI paradigm in prairie voles following 4 weeks of social isolation or pairing plus daily exogenous administration of either oxytocin (20 μg/50 μl/vole, sc) or sterile saline vehicle (50 μl/vole, sc).

	Aggressive episodes (number)	Activity (cpm)
Paired+V (n = 7)	2.1 ± 0.9	39.3 ± 4.5
Paired+OT (n = 6)	4.0 ± 0.8	40.5 ± 5.6
Isolated+V (n = 7)	3.1 ± 1.3	40.9 ± 5.4
Isolated+OT (n = 6)	4.2 ± 1.2	36.9 ± 5.3

Note: Values represent mean ± SEM. Abbreviations: cpm, counts per minute; OT, oxytocin; SEM, standard error of the mean; V, vehicle.

Figure 2.  Mean ( + SEM) HR (Panel A), SDNN Index (Panel B), and amplitude of RSA (Panel C) before, during, and following the 5-min resident–intruder paradigm in prairie voles following 4 weeks of social isolation or pairing plus daily exogenous administration of either oxytocin (20 μg/50 μl/vole, sc) or sterile saline vehicle (50 μl/vole, sc), in the following groups: Paired+V (‐‐▴‐‐; n = 6), Paired+OT (—▴—; n = 5), Isolated+V (‐‐▪‐‐; n = 7), and Isolated+OT (—▪—; n = 5). Three-factor mixed-design ANOVA with post-hoc multiple comparisons: ^*P < 0.05 versus Paired+V, Paired+OT, and Isolated+OT groups at the same time point; ^†P < 0.05 versus two paired groups at the same time point; ^¶P < 0.05 versus Paired+V and Isolated+OT groups at the same time point; ^‡P < 0.05 versus respective RI test value. Abbreviations: ANOVA, analyses of variance; HR, heart rate; OT, oxytocin; RI test, resident–intruder paradigm; RSA, respiratory sinus arrhythmia; SDNN, SD of normal-to-normal intervals; V, vehicle.

Figure 3.  Coronal brain sections (40 μm) from a representative subject in each group showing the density of immunoreactive cell bodies (number of cell bodies per standardized area; oxytocin, Panel A; CRH, Panel B), and mean ( + SEM) group data (oxytocin, Panel C; CRH, Panel D), in the PVN of the hypothalamus of paired and isolated prairie voles following 4 weeks of social isolation or pairing plus daily exogenous administration of either oxytocin (20 μg/50 μl/vole, sc) or sterile saline vehicle (50 μl/vole, sc), in the following groups: Paired+V (n = 7), Paired+OT (n = 6), Isolated+V (n = 7), and Isolated+OT (n = 6). Scale bars = 100 μm. Two-way independent-groups ANOVA with Bonferroni-corrected t-tests for multiple comparisons: ^*P < 0.05 versus Paired (Pair) + V, Paired+OT, and Isolated (Isol) + OT groups; ^†P < 0.05 versus two vehicle-treated groups. Abbreviations: ANOVA, analyses of variance; CRH, corticotropin-releasing hormone; ir, immunoreactive; OT, oxytocin; V, vehicle.