Are behavioral effects of early experience mediated by oxytocin?

Abstract

Early experiences can alter adaptive emotional responses necessary for social behavior as well as physiological reactivity in the face of challenge. In the highly social prairie vole (Microtus ochrogaster), manipulations in early life or hormonal treatments specifically targeted at the neuropeptides oxytocin (OT) and arginine vasopressin (AVP), have long-lasting, often sexually dimorphic, consequences for social behavior. Here we examine the hypothesis that behavioral changes associated with differential early experience, in this case handling the family during the first week of life, may be mediated by changes in OT or AVP or their brain receptors. Four early treatment groups were used, differing only in the amount of manipulation received during the first week of life. MAN1 animals were handled once on post-natal day 1; MAN1 treatment produces a pattern of behavior usually considered typical of this species, against which other groups were compared. MAN1-7 animals were handled once a day for post-natal days 1-7, MAN 7 animals were handled once on post-natal day 7, and MAN0 animals received no handling during the first week of life. When tested following weaning, males in groups that had received manipulation during the first few days of life (MAN1 and MAN1-7) displayed higher alloparenting than other groups. Neuroendocrine measures, including OT receptor binding and OT and AVP immunoreactivity, varied by early treatment. In brain areas including the nucleus accumbens, bed nucleus of stria terminalis and lateral septum, MAN0 females showed increased OT receptor binding. MAN1 animals also displayed higher numbers of immunoreactive OT cell bodies in the supraoptic nucleus. Taken together these findings support the broader hypothesis that experiences in the first few days of life, mediated in part by sexually dimorphic changes in neuropeptides, especially in the receptor for OT, may have adaptive consequences for sociality and emotion regulation.

Keywords: anxiety; monogamy; oxytocin; parental care; vasopressin.

Figure 1

Males that were manipulated before day 7 displayed a significantly longer duration of non-huddling contact (F₁ = 4. 95, p = 0.035; Table 1) and total time spent in alloparental behavior (F₁ = 4.24, p = 0.046).

Figure 2

Time spent autogrooming in the elevated plus-maze differed among treatment groups in females (F₃ = 4. 38, p = 0.012). There was a trend for time spent in the closed arms to differ (Kruskal–Wallis test, χ² = 7.14, p = 0.067). Groups which differ significantly from each other in the overall ANOVA are indicated by different letters. When MAN1 and MAN0 females were compared directly in pre-planned comparisons, MAN1 females autogroomed significantly more than MAN0 females (F₁ = 4.87, p = 0.041) and MAN1 females tended to spend more time in the closed arms than MAN0 females (F₁ = 3.38, p = 0.084).

Figure 3

Oxytocin receptor binding (optical density), females. Bars with different letters indicate groups that are significantly different in post hoc testing.

Figure 4

Representative autoradiogram of OTR binding in MAN1 and MAN0 females.

Figure 5

Oxytocin receptor binding (optical density), males. Bars with different letters indicate groups that are significantly different in post hoc testing.

Figure 6

The number of OT cell bodies in the SON differed significantly by treatment for males (F₃ = 5. 46, p = 0.005). Although the overall ANOVA for females was not significant (F₃ = 1.9, p = 0.157), there was a trend for a difference between MAN0 and MAN1 (t₁ = −1.73, p = 0.096).

Figure 7

Representative photographs of OT immunoreactivity in the SON in MAN1 and MAN0 animals.

Figure 8

There is a trend for stress-induced corticosterone to differ in females (F₃ = 2. 41, p = 0.085) but not in males (F₃ = 0.68, p = 0.569).

Figure 9

Plasma AVP did not differ significantly by treatment following the EPM test in males (F₃ = 0.33, p = 0.802) or females (F₃ = 0.07, p = 0.977).

Figure 10

Plasma OT did not differ significantly by treatment in males (F₃ = 1. 63, p = 0.199) or females (F₃ = 1.23, p = 0.316).