title: Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin.
abstract: Social behaviours in species as diverse as honey bees and humans promote group survival but often come at some cost to the individual. Although reinforcement of adaptive social interactions is ostensibly required for the evolutionary persistence of these behaviours, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin acts as a social reinforcement signal within the nucleus accumbens core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the nucleus accumbens receives oxytocin-receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-hydroxytryptamine; 5-HT) innervation to the nucleus accumbens, abolishes the reinforcing properties of social interaction. Furthermore, oxytocin-induced synaptic plasticity requires activation of nucleus accumbens 5-HT1B receptors, the blockade of which prevents social reward. These results demonstrate that the rewarding properties of social interaction in mice require the coordinated activity of oxytocin and 5-HT in the nucleus accumbens, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.
authors.affiliation: Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, California 94305, USA.
authors.forename: Gül
authors.initials: G
authors.lastname: Dölen
authors.forename: Ayeh
authors.initials: A
authors.lastname: Darvishzadeh
authors.forename: Kee Wui
authors.initials: KW
authors.lastname: Huang
authors.forename: Robert C
authors.initials: RC
authors.lastname: Malenka
mesh_terms: D000818:Animals; D001321:Autistic Disorder / Q000503:physiopathology; D003213:Conditioning, Psychological; D005260:Female; D017353:Gene Deletion; D036881:Long-Term Synaptic Depression; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D009714:Nucleus Accumbens / Q000166:cytology / Q000378:metabolism*; D010121:Oxytocin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D017729:Presynaptic Terminals / Q000378:metabolism; D011903:Raphe Nuclei / Q000378:metabolism; D044302:Receptor, Serotonin, 5-HT1B / Q000378:metabolism; D018045:Receptors, Oxytocin / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012201:Reward; D012701:Serotonin / Q000378:metabolism*; D012919:Social Behavior; D009435:Synaptic Transmission
chemical_list: D044302:Receptor, Serotonin, 5-HT1B; D018045:Receptors, Oxytocin; D012701:Serotonin; D010121:Oxytocin
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