Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin

Abstract

Social behaviors 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 behaviors, the neural mechanisms by which social reward is encoded by the brain are largely unknown. Here we demonstrate that in mice oxytocin (OT) acts as a social reinforcement signal within the nucleus accumbens (NAc) core, where it elicits a presynaptically expressed long-term depression of excitatory synaptic transmission in medium spiny neurons. Although the NAc receives OT receptor-containing inputs from several brain regions, genetic deletion of these receptors specifically from dorsal raphe nucleus, which provides serotonergic (5-HT) innervation to the NAc, abolishes the reinforcing properties of social interaction. Furthermore, OT-induced synaptic plasticity requires activation of NAc 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 OT and 5-HT in the NAc, a mechanistic insight with implications for understanding the pathogenesis of social dysfunction in neuropsychiatric disorders such as autism.

Insular Cortex Mediates Approach and Avoidance Responses to Social Affective Stimuli

“…Indeed, OT has been shown to increase spike output 89-91 and facilitate synaptic long-term potentiation 92-94 and our data suggest an intrinsic mechanism that may underlie shifts in synaptic efficacy and excitatory/inhibitory balance found in brain regions where OT is critical for myriad social behaviors 67,74,90,95 . Intrinsic properties are shaped by ion channels.…”

“…After achieving a whole-cell configuration, baseline recordings were made in aCSF until 10 minutes of stable baseline were observed, at which point 500 nM oxytocin citrate was added to the bath. The dose of 500 nM was selected after a pilot study using a range of doses from 50nM to µ1M, the largest dose reported 95 . Because OT has high affinity for the Vasopressin 1A receptor (V1a), experiments typically isolate effects of OT to the OTR by using synthetic OTR agonists or a cocktail of OT and V1a antagonists.…”

Activating positive memory engrams suppresses depression-like behaviour

“…The NAC has been heavily implicated in stress responses, mood disorders, and processing natural rewards 2,5,[11][12][13][16][17][18][19][20][21] . Moreover, pathophysiological dysfunction of the NAcc in response to various stressors has been implicated in anhedonia and reward conditioning [18][19][20][21] .…”

Endocannabinoid signaling mediates oxytocin-driven social reward

“…Moreover, the receptors and their endogenous lipid-derived ligands, anandamide and 2-arachidonoyl-sn-glycerol (2-AG) (8), have been implicated in the control of social play (9) and social anxiety (10,11), two crucial aspects of the social experience. Another essential facet of social behavior, the adaptive reinforcement of interactions among members of a group (i.e., the reward of being social), requires the oxytocin-dependent induction of long-term synaptic plasticity at excitatory synapses of the nucleus accumbens (NAc) (12), a key region in the brain reward circuit. Because the endocannabinoid system regulates the reinforcement of various natural stimuli (13) as well as NAc neurotransmission (14), in the present study we tested the hypothesis that this signaling complex might cooperate with oxytocin to control social reward.…”