Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior

Abstract

Oxytocin is produced in the hypothalamus and released into the circulation through the neurohypophyseal system. Peripherally released oxytocin facilitates parturition and milk ejection during nursing. Centrally released oxytocin coordinates the onset of maternal nurturing behavior at parturition and plays a role in mother-infant bonding. More recent studies have revealed a more general role for oxytocin in modulating affiliative behavior in both sexes. Oxytocin regulates alloparental care and pair bonding in female monogamous prairie voles. Social recognition in male and female mice is also modulated by oxytocin. In humans, oxytocin increases gaze to the eye region of human faces and enhances interpersonal trust and the ability to infer the emotions of others from facial cues. While the neurohypopheseal oxytocin system has been well characterized, less is known regarding the nature of oxytocin release within the brain. Here we review the role of oxytocin in the regulation of prosocial interactions, and discuss the neuroanatomy of the central oxytocin system.

Figure 1

OTR and alloparental behavior in female prairie voles. Autoradiography showing oxytocin receptor density in the nucleus accumbens (NAcc) and caudate putamen (CP) in non-maternal (A) and spontaneously maternal (B) female prairie voles. Females that have a high density of OTR in the NAcc are more likely to exhibit alloparental care than those with a low level of accumbal OTR. C) Graph showing the effect of administering oxytocin antagonist (OTA) or cerebral spinal fluid (CSF) into the NAcc or CP on alloparental behavior of female prairie voles. Nulliparous females injected with CSF in the NAcc or CP, or OTA in the CP, showed the normal variation in propensity for alloparental behavior, with about half showing nurturing care. However, injecting OTA into the NAcc inhibited alloparental behavior in all the females, suggesting that endogenous oxytocin is necessary for the expression of alloparental behavior in female prairie voles. Adapted from [44] with permission.

Figure 2

Infant-mother interactions of oxytocin knock-out (OTKO) pups. Ten day old pups were place in one chamber of a testing arena in which the mother was restricted to a second chamber. The divider contained small holes that were large enough for the pup to pass through, but that prevented the mother from entering. The latency for the pup to enter the mother's chamber was recorded on three successive trials. There was no difference between wildtype and OTKO pups in the initial training trial. However, in the subsequent trials OTKO pups exhibited a significantly longer latency than wild-type pups to cross into the mother's chamber (p < 0.05). Thus OT may be involved in motivating pups to seek contact with their caregiver.

Figure 3

Species differences in oxytocin receptor (OTR) expression in prairie and montane voles. Notice the higher level of OTR binding in the caudate (CP) and nucleus accumbens (NAcc) of the prairie vole (A) than the montane vole (B). Both species have OTR binding in the prefrontal cortex (PFC) C) Graph illustrating the effects of administering oxytocin antagonist (OTA) or cerebral spinal fluid (CSF) into the PFC, CP, or NAcc on pair bonding behavior in female prairie voles. Administering OTA into the CP or CSF during a 24-hour cohabitation with mating, does not effect the formation of a partner preference. However, injecting OTA into the PFC or NAcc blocked females from bonding with their mating partner, showing that oxytocin in these areas is important for affiliative behavior in a monogamous vole. Adapted from [55, 58] with permission.

Figure 4

Viral vector mediated over-expression of oxytocin receptor (OTR) in the nucleus accumbens (NAcc) of female prairie voles enhances partner preference formation. Shown is the OTR binding density in female prairie voles receiving bilateral injection into the NAcc of an adeno-associated viral vector expressing green fluorescent protein (GFP) (A) or the prairie vole OTR gene. C) After a cumulative 18 h cohabitation with a male partner, females over-expressing OTR in the NAcc spent significantly more time with the partner, than the stranger, during a partner preference test (p<0.001). The GFP injected females did not spend significantly more time with either male. Adapted from [144] with permission.

Figure 5

Light micrograph of oxytocin-immunoreactive fibers in the prairie vole from a horizontal section. Notice that a few fibers deviate from the neurohypophysial pathway of the paraventricular nucleus of the hypothalamus (PVN) and project toward the nucleus accumbens (NAcc). Scale bar = 100 μm. ac = anterior commisure, f = fornix. Reprinted from [59] with permission.

Figure 6

Oxytocin receptor binding (A-C) and oxytocin-immunoreactive fiber distribution (D-F) in rats (top), mice (middle) and prairie voles (bottom). Note the remarkable species differences in oxytocin receptor binding in the nucleus accumbens (NAcc), but similarity in oxytocin-immunoreactive fibers. ac = anterior commisure. Adapted from [1, 59] with permission.

Figure 7

Models of the possible origin of the oxytocin (OT)-immunoreactive processes in NAcc. A) Separate neuronal populations comprise the neurohyphyseal OT system and the centrally projecting system. Magnocellular (mag) neurons project to the posterior pituitary while parvocellular (pv) neurons project to specific brain regions. This is the prevailing view of many investigators. B) Somatodendritically released OT from magnocellular hypothalamic neurons diffuses to distant brain regions in a paracrine fashion. C) Centrally projecting OT fibers may be axon collaterals of neurohyphyseal OT neurons that are projecting towards the pituitary. From our research in prairie voles, this model is most likely. Note that in models A and C, OT may influence OT receptor populations by either direct release from local processes, or after diffusion following somatodendritic release within the hypothalamus.