Review
Dopaminergic-neuropeptide interactions in the social brain

https://doi.org/10.1016/j.tics.2008.09.007Get rights and content

A well-mapped set of brain regions is dedicated to social cognition. It is responsive to social cues, engaged in moral decision-making and makes predictions about the likely behaviour of other people. Recent studies of affiliation, using animal models, have revealed that specific neurotransmitters and hormones influence the neural circuits of ‘the social brain’. There is converging evidence that the interface between the neuropeptides oxytocin and vasopressin and dopaminergic reward circuits is of particular importance. In the context of recent research, we discuss emerging evidence for the impact of these neuropeptides on the regulation of the social brain. We also examine the putative role of allelic variation in candidate genes on individual differences in social cognitive processing and associated social behaviour.

Introduction

Social interaction in humans is complex, compared with the social relationships between other animal species. The way in which we relate to others involves many disparate neural functions, including representations of internal somatic states, knowledge about the self, social perceptions and interpersonal motivations. All are orchestrated to support normal, skilled social adaptation. Underpinning social responsiveness is a set of skills termed ‘social cognition’. Successful social interactions require us to observe other people's behaviour, to predict the behaviour of others in relation to ourselves [1] and to respond appropriately. As children, we become increasingly aware of our own actions and their impact on the physical and social world. Social understanding, language and imitation are probably learned through neural systems that respond both during our own actions and when we see others behaving in a similar way [2]. The development of social cognition involves the coordinated action of a network of cortical loci, the original components of which were outlined by Brothers [3]. They included the amygdala, orbito-frontal cortex and aspects of the temporal cortex (the temporo-parietal junction, posterior superior temporal sulcus and the temporal poles) to which we now add the medial prefrontal cortex, the adjacent paracingulate cortex and the ‘mirror’ system [4]. We discuss emerging evidence for a range of genetic and hormonal influences on the coordinated functioning of these regions.

Section snippets

Neural circuits of the social brain

The neural interconnectivity of the ‘social brain’ is outlined schematically in Figure 1 and discussed in Box 1. The amygdala is central to the schema because of its role in associating social stimuli (auditory, visual and olfactory) with value [5]. Accordingly, it directs our unconscious responses during social encounters [1] and alerts us to potential threats posed by sensory stimuli (in addition to being aroused by sexual imagery). The reciprocal connections of the amygdala with the primary

OT and AVP

OT and AVP are neuropeptides, differing in structure by just two of nine amino acids. Nonapeptides similar to OT and AVP are found in diverse species, and their relative chemical similarity indicates that they have long been conserved during evolution. Both have widespread receptor-mediated effects on behaviour and physiology [12]. The sex steroids estrogen and androgen, respectively, modulate their synthesis and their receptors (although species-specific differences occur) and thereby

OT

OT is synthesized in the magnocellular neurosecretory cells that are located in the supraoptic and paraventricular nuclei of the hypothalamus, and in the parvocellular neurons of the paraventricular nuclei. Projections from the magnocellular cells of the hypothalamus link to the posterior pituitary, from which OT is released into the general circulation. The parvocellular neurons of the paraventricular nuclei project to the limbic system (hippocampus, amygdala, striatum, hypothalamus and

AVP

AVP is synthesized primarily in the magnocellular cells of the supraoptic and paraventricular nuclei of the hypothalamus [41]. From here, axons project to the posterior pituitary from where it is released into general circulation. It acts primarily as an antidiuretic hormone. There are also several populations of smaller, parvocellular neurons within the paraventricular nuclei, the bed nucleus of the stria terminalis, the medial amygdala and suprachiasmatic nucleus [42] in which synthesis is

Interaction between dopaminergic, OT and AVP systems

Evidence for the importance of interaction between the dopaminergic, OT and AVP systems, exists in several brain areas and at several levels. There is little doubt that, in humans, activity in dopaminergic reward pathways is associated with socially affiliative behaviours, and it is modulated by OT and AVP activity. This modulation does not necessarily imply that the receptors for dopamine, OT and AVP are proximal to one another in the brain. It is possible that interactions between

Conclusions

Underlying social cognition is a coordinated neural network. The normal functioning of that network engages the neuropeptides OT and AVP with activity of dopaminergic receptors in the striatum and the orbitofrontal cortex 63, 69. Together, their actions permit social recognition, trust and a range of socially affiliative behaviours. Sexual dimorphism in aggression, parenting style and pair-bonding reflects differential activity in this system, which is modulated by sex steroids: in males

Acknowledgements

D.H.S. was supported by the Wellcome Trust, the Nancy Lurie Marks Family Foundation, the Simons Foundation and the European Commission (Framework 6) during the preparation of this article. L.G. was supported by the Health Research Board of Ireland and Autism Speaks during the preparation of this article.

References (94)

  • E.B. Keverne et al.

    Vasopressin, oxytocin and social behaviour

    Curr. Opin. Neurobiol.

    (2004)
  • Y. Liu et al.

    Nucleus accumbens oxytocin and dopamine interact to regulate pair bond formation in female prairie voles

    Neuroscience

    (2003)
  • J.R. Williams

    Development of partner preferences in female prairie voles (Microtus ochrogaster): the role of social and sexual experience

    Horm. Behav.

    (1992)
  • S.W. Porges

    The polyvagal perspective

    Biol. Psychol.

    (2007)
  • A.J. Guastella

    Oxytocin increases gaze to the eye region of human faces

    Biol. Psychiatry

    (2008)
  • M. Heinrichs

    Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress

    Biol. Psychiatry

    (2003)
  • E. Hollander

    Oxytocin increases retention of social cognition in autism

    Biol. Psychiatry

    (2007)
  • S. Wu

    Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population

    Biol. Psychiatry

    (2005)
  • S. Jacob

    Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism

    Neurosci. Lett.

    (2007)
  • H.K. Caldwell

    Vasopressin: behavioral roles of an “original” neuropeptide

    Prog. Neurobiol.

    (2008)
  • G.J. De Vries et al.

    Sexual differentiation of central vasopressin and vasotocin systems in vertebrates: different mechanisms, similar endpoints

    Neuroscience

    (2006)
  • K.L. Bales

    Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors

    Neuroscience

    (2007)
  • M. Saito

    Molecular cloning and characterization of rat V1b vasopressin receptor: evidence for its expression in extra-pituitary tissues

    Biochem. Biophys. Res. Commun.

    (1995)
  • E.E. Storm et al.

    Social circuits: peptidergic regulation of mammalian social behavior

    Neuron

    (2005)
  • F. Loup

    Localization of high-affinity binding sites for oxytocin and vasopressin in the human brain. An autoradiographic study

    Brain Res.

    (1991)
  • I.F. Bielsky

    The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study

    Neuron

    (2005)
  • I.F. Bielsky

    Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice

    Behav. Brain Res.

    (2005)
  • W.S. Young

    The vasopressin 1b receptor is prominent in the hippocampal area CA2 where it is unaffected by restraint stress or adrenalectomy

    Neuroscience

    (2006)
  • K. Mishima

    Ameliorative effect of NC-1900, a new AVP4-9 analog, through vasopressin V1A receptor on scopolamine-induced impairments of spatial memory in the eight-arm radial maze

    Neuropharmacology

    (2003)
  • V. Paban

    Behavioral effects of arginine8-vasopressin in the Hebb-Williams maze

    Behav. Brain Res.

    (2003)
  • H.K. Caldwell

    The acute intoxicating effects of ethanol are not dependent on the vasopressin 1a or 1b receptors

    Neuropeptides

    (2006)
  • J.G. Goekoop

    Depression with above-normal plasma vasopressin: validation by relations with family history of depression and mixed anxiety and retardation

    Psychiatry Res.

    (2006)
  • J. Rilling

    A neural basis for social cooperation

    Neuron

    (2002)
  • S. Zeki

    The neurobiology of love

    FEBS Lett.

    (2007)
  • R. Adolphs et al.

    Role of the amygdala in processing visual social stimuli

    Prog. Brain Res.

    (2006)
  • E.J. Nestler et al.

    The mesolimbic dopamine reward circuit in depression

    Biol. Psychiatry

    (2006)
  • E.T. Rolls

    The representation of information about faces in the temporal and frontal lobes

    Neuropsychologia

    (2007)
  • M.R. Delgado

    An fMRI study of reward-related probability learning

    Neuroimage

    (2005)
  • J.T. Curtis

    Dopamine and monogamy

    Brain Res.

    (2006)
  • L.J. Young

    Cellular mechanisms of social attachment

    Horm. Behav.

    (2001)
  • A. Bartels et al.

    The neural correlates of maternal and romantic love

    Neuroimage

    (2004)
  • G. Rizzolatti et al.

    The mirror-neuron system

    Annu. Rev. Neurosci.

    (2004)
  • R.J. Dolan

    The human amygdala and orbital prefrontal cortex in behavioural regulation

    Philos. Trans. R. Soc. Lond. B Biol. Sci.

    (2007)
  • M. Iacoboni et al.

    The mirror neuron system and the consequences of its dysfunction

    Nat. Rev. Neurosci.

    (2006)
  • V. Gallese

    Intentional attunement: mirror neurons and the neural underpinnings of interpersonal relations

    J. Am. Psychoanal. Assoc.

    (2007)
  • D.M. Amodio et al.

    Meeting of minds: the medial frontal cortex and social cognition

    Nat. Rev. Neurosci.

    (2006)
  • L.J. Young et al.

    The neurobiology of pair bonding

    Nat. Neurosci.

    (2004)
  • Cited by (290)

    View all citing articles on Scopus
    View full text