RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles

Keebaugh, Alaine C.; Barrett, Chris; LaPrairie, Jamie L.; Jenkins, Jasmine J; Young, Larry J.

doi:10.1080/17470919.2015.1040893

Cited by 129 publications

(123 citation statements)

References 67 publications

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“…This work indicates critical roles of multiple neurochemical systems in the regulation of behaviors associated with pair-bonding including oxytocin (Bales et al, 2007b; Keebaugh et al, 2015; Ross et al, 2009; Williams et al, 1994), vasopressin (Lim et al, 2004; Lim and Young, 2004; Pitkow et al, 2001), dopamine (Aragona and Wang, 2009; Hostetler et al, 2011; Resendez et al, 2016), and opioid systems (Burkett et al, 2011; Resendez et al, 2013; Resendez et al, 2016; Resendez et al, 2012). In contrast, no work to our knowledge has examined serotonergic involvement in pair-bonding in the prairie vole, and little work has examined serotonergic influences on social behavior more generally in this species.…”

Section: Introductionmentioning

confidence: 89%

Serotonin 1A agonism decreases affiliative behavior in pair-bonded titi monkeys

Larke

Maninger

Ragen

et al. 2016

Hormones and Behavior

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Relatively little is known about serotonergic involvement in pair-bonding despite its putative role in regulating social behavior. Here we sought to determine if pharmacological elevation of serotonin 1A (5-HT1A) receptor activity would lead to changes in social behavior in pair-bonded male titi monkeys (Callicebus cupreus). Adult males in established heterosexual pairs were injected daily with the selective 5-HT1A agonist 8-OH-DPAT or saline for 15 days using a within-subjects design. Social behavior with the female pair-mate was quantified, and plasma concentrations of oxytocin, vasopressin, and cortisol were measured. When treated with saline, subjects showed reduced plasma oxytocin concentrations, while 8-OH-DPAT treatment buffered this decrease. Treatment with 8-OH-DPAT also led to decreased plasma cortisol 15 minutes post-injection and decreased social behavior directed toward the pair-mate including approaching, initiating contact, lipsmacking, and grooming. The reduction in affiliative behavior seen with increased activity at 5-HT1A receptors indicates a substantial role of serotonin activity in the expression of social behavior. In addition, results indicate that the effects of 5-HT1A agonism on social behavior in adulthood differ between rodents and primates.

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Section: Introductionmentioning

confidence: 89%

Serotonin 1A agonism decreases affiliative behavior in pair-bonded titi monkeys

Larke

Maninger

Ragen

et al. 2016

Hormones and Behavior

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“…5–7 Further evidence for the critical role of OXTR in social functioning comes from animal models demonstrating that dense expression of the oxytocin receptor in the nucleus accumbens (NAcc) is associated with social affiliative behaviors, 8 reduces susceptibility to early adverse experiences (for example, neglect) 9 and critically, that allelic variation in the OXTR is associated with variability in receptor expression specifically in brain areas important for social attachment, including the NAcc. 10 Further, disruption of oxytocin receptor signaling in the NAcc inhibits social attachment 11,12 and the formation of positive associations with social rewards. 13 Together, these studies suggest that oxytocin receptor function in the NAcc is required to form associations with social rewards through its effects on neural excitability in reward-related brain regions.…”

Section: Introductionmentioning

confidence: 99%

Additive effects of oxytocin receptor gene polymorphisms on reward circuitry in youth with autism

et al. 2016

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Several common alleles in the oxytocin receptor gene (OXTR) are associated with altered brain function in reward circuitry in neurotypical adults and may increase risk for autism spectrum disorders (ASD). Yet, it is currently unknown how variation in the OXTR relates to brain functioning in individuals with ASD, and, critically, whether neural endophenotypes vary as a function of aggregate genetic risk. Here, for we believe the first time, we use a multi-locus approach to examine how genetic variation across several OXTR single-nucleotide polymorphisms (SNPs) affect functional connectivity of the brain’s reward network. Using data from 41 children with ASD and 41 neurotypical children, we examined functional connectivity of the nucleus accumbens (NAcc) – a hub of the reward network – focusing on how connectivity varies with OXTR risk-allele dosage. Youth with ASD showed reduced NAcc connectivity with other areas in the reward circuit as a function of increased OXTR risk-allele dosage, as well as a positive association between risk-allele dosage and symptom severity, whereas neurotypical youth showed increased NAcc connectivity with frontal brain regions involved in mentalizing. In addition, we found that increased NAcc-frontal cortex connectivity in typically developing youth was related to better scores on a standardized measure of social functioning. Our results indicate that cumulative genetic variation on the OXTR impacts reward system connectivity in both youth with ASD and neurotypical controls. By showing differential genetic effects on neuroendophenotypes, these pathways elucidate mechanisms of vulnerability versus resilience in carriers of disease-associated risk alleles.

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“…For example, recent research showed that genetic variations in the OT-receptor gene (OXTR) of prairie voles are related to social attachment and partner preference (King et al, 2015), and that knock-down of the OT receptor inhibited social attachment and parental care (Keebaugh et al, 2015). Also in human infants, polymorphisms in the OXTR gene have been associated with variations in attachment security (Chen et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

Long-term oxytocin administration enhances the experience of attachment

Bernaerts

Prinsen

Berra

et al. 2017

Psychoneuroendocrinology

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Oxytocin and attachment -Bernaerts et al. 2 Highlights We examined effects of multiple-dose intranasal oxytocin (OT) on attachment  State and Trait attachment were assessed before and after two-week OT administration  OT treatment decreased attachment avoidance and increased attachment toward peers  Participants with less secure peer attachment showed most pronounced OT effects  OT treatment was also associated with changes in mood ABSTRACTThe neuropeptide 'oxytocin' (OT) is known to play a pivotal role in a variety of complex social behaviors by promoting a prosocial attitude and interpersonal bonding. Previous studies showed that a single-dose of exogenously administered OT can affect trust and feelings of attachment insecurity. With the present study, we explored the effects of two weeks of daily OT administration on measures of state and trait attachment using a double-blind betweensubjects randomized placebo-controlled design. In 40 healthy young adult men state and trait attachment were assessed before and after two weeks of daily intranasal OT (24 IU) or placebo using the State Adult Attachment Scale and the Inventory of Parent and Peer Attachment.Mood, social responsiveness and quality of life were additionally assessed as secondary outcome measures. Reductions in attachment avoidance and increases in reports of attachment toward peers were reported after two weeks of OT treatment. Further, treatmentinduced changes were most pronounced for participants with less secure attachment towards their peers. indicating that normal variance at baseline modulated treatment response. OT treatment was additionally associated with changes in mood, indicating decreases in feelings of tension and (tentatively) anger in the OT group, not in the placebo group. Further, at the end of the two-week trial, both treatment groups (OT, placebo) reported to experience an increase in social responsiveness and quality of life, but the effects were only specific to the OTtreatment in terms of reports on 'social motivation'. In summary, the observed improvements on state and trait dimensions of attachment after a multiple-dose treatment with OT provide further evidence in support of a pivotal role of OT in promoting the experience of attachment. KEYWORDSOxytocin, State attachment, Trait attachment, Mood, Social responsiveness, Quality of life Oxytocin and attachment -Bernaerts et al.3

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RNAi knockdown of oxytocin receptor in the nucleus accumbens inhibits social attachment and parental care in monogamous female prairie voles

Cited by 129 publications

References 67 publications

Serotonin 1A agonism decreases affiliative behavior in pair-bonded titi monkeys

Serotonin 1A agonism decreases affiliative behavior in pair-bonded titi monkeys

Additive effects of oxytocin receptor gene polymorphisms on reward circuitry in youth with autism

Long-term oxytocin administration enhances the experience of attachment

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