Sex differences and developmental effects of manipulations of oxytocin on alloparenting and anxiety in prairie voles

Abstract

In adult animals, peptide hormones, including oxytocin and arginine vasopressin, have been implicated in both parental behavior and the modulation of anxiety. The purpose of this study was to examine the consequences of developmental manipulations of oxytocin for the later expression of alloparental behavior as well as behavioral responses to a novel environment, the elevated plus maze (EPM). Prairie voles (Microtus ochrogaster), a cooperatively breeding species, were selected for this study. On neonatal Day 1, pups received an ip injection of oxytocin or oxytocin antagonist, or were controls, receiving either saline or handling only. At 21 and approximately 60 days of age, each animal was tested for parental care toward novel stimulus pups. At approximately 67 days, an EPM test was administered. Control females at 60 days of age were more likely to attack pups and spent less time in the open arm of the EPM, both of which might reflect higher levels of anxiety in females than males. In males, neonatal treatment with oxytocin antagonist was associated with reductions in parental care, especially during the initial exposure to pups on Day 21. Female behavior was not significantly changed as a function of neonatal treatments. Findings to date implicate vasopressin in the behavioral changes in males, that in later life followed a single exposure to an oxytocin antagonist, and suggest caution in the clinical use of agents such as Atosiban, which may have the potential to influence infant development.

Oxytocin has dose-dependent developmental effects on pair-bonding and alloparental care in female prairie voles

“…For example, in male prairie voles neonatal OT facilitated pair-bond formation (Bales and Carter, 2003b); neonatal OT was also associated with a later, sexually dimorphic increase in AVP (V1a) receptor binding in the ventral pallidum and cingulate cortex (Bales et al, 2007b). Males of this species treated with an OTA (at 0.1 mg/kg) exhibited decreased levels of parental care (Bales et al, 2004c), a tendency to be less aggressive (Bales and Carter, 2003a), and as adults showed lower levels of V1a binding in the bed nucleus of the stria terminalis, the lateral septum, and the medial preoptic area (Bales et al, 2007b).…”

“…For example, in male prairie voles neonatal OT facilitated pair-bond formation (Bales and Carter, 2003b); neonatal OT was also associated with a later, sexually dimorphic increase in AVP (V1a) receptor binding in the ventral pallidum and cingulate cortex (Bales et al, 2007b). Males of this species treated with an OTA (at 0.1 mg/kg) exhibited decreased levels of parental care (Bales et al, 2004c), a tendency to be less aggressive (Bales and Carter, 2003a), and as adults showed lower levels of V1a binding in the bed nucleus of the stria terminalis, the lateral septum, and the medial preoptic area (Bales et al, 2007b).In females neonatal treatment with OT (1 mg/kg) was associated in adulthood with an increase in female-female aggression after exposure to a male ("mate-guarding"); however, other behaviors including partner preferences and parental care were not measurably affected by this treatment (Bales and Carter, 2003a;Bales et al, 2004c). Thus, in this series of studies of the developmental effects of OT the most marked behavioral changes were observed in males (Carter, 2003).…”

Developmental Perspectives on Oxytocin and Vasopressin

“…Early postnatal manipulations of prairie voles with oxytocin or an oxytocin antagonist have sexually dimorphic effects on later behavior, with males seemingly more affected by such perinatal treatments (reviewed in Carter et al, 2009). A single postnatal injection of oxytocin in male prairie voles increased the probability of partner preference and reduced anxiety-like behavior in adulthood (Bales and Carter, 2003), and a neonatal dose of OXTR antagonist reduced alloparental behavior in adult male prairie voles, without affecting partner preference behavior (Bales et al, 2004). The same perinatal dose in females did not affect partner preference behavior in adulthood, although higher doses did affect partner preference behavior, but in a non-linear manner (Bales et al, 2007b;Carter et al, 2009).…”

Hormonal mechanisms of cooperative behaviour

“…Both OT and AVP have organizational effects on the brain both during the neonatal as well as postnatal periods in rodents, with sex-specific effects (Cushing & Kramer 2005). In prairie voles, a single injection of OT on the day of birth affects aggressive behaviour (Carter 2003) and male alloparenting rates (Bales et al 2004). Likewise, administration of AVP soon after birth increases aggressive behaviour in adult male prairie voles (Stribley & Carter 1999) and changes risk-taking and social behaviour in rats (Boer et al 1994).…”