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

Social Neuroscience

Volumn 10, Issue 5, 2015, Pages 561-570

  Keebaugh, Alaine C ^a   Barrett, Catherine E ^a   Laprairie, Jamie L ^a   Jenkins, Jasmine J ^b   Young, Larry J ^a  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b GEORGIA STATE UNIVERSITY   (United States)

Author keywords

Alloparental care; Pair bonding; Striatum

Indexed keywords

GREEN FLUORESCENT PROTEIN; MESSENGER RNA; OXYTOCIN RECEPTOR; SMALL INTERFERING RNA;

ANALYSIS OF VARIANCE; ANIMAL; ARVICOLINAE; AUTORADIOGRAPHY; DEFICIENCY; FEMALE; GENE VECTOR; GENETIC TRANSDUCTION; GENETIC TRANSFECTION; GENETICS; HEK293 CELL LINE; HUMAN; METABOLISM; NEWBORN; NUCLEUS ACCUMBENS; OBJECT RELATION; PAIR BONDING; PARENT; PHYSIOLOGY; PSYCHOLOGY; RNA INTERFERENCE;

ANALYSIS OF VARIANCE; ANIMALS; ANIMALS, NEWBORN; ARVICOLINAE; AUTORADIOGRAPHY; FEMALE; GENETIC VECTORS; GREEN FLUORESCENT PROTEINS; HEK293 CELLS; HUMANS; NUCLEUS ACCUMBENS; OBJECT ATTACHMENT; PAIR BOND; PARENTS; RECEPTORS, OXYTOCIN; RNA INTERFERENCE; RNA, MESSENGER; RNA, SMALL INTERFERING; TRANSDUCTION, GENETIC; TRANSFECTION;

EID: 84945486926     PISSN: 17470919     EISSN: 17470927     Source Type: Journal    
DOI: 10.1080/17470919.2015.1040893     Document Type: Article

References (61)

1. T.H.Ahern,, E.A.D.Hammock,, & L.J.Young, (2011). Parental division of labor, coordination, and the effects of family structure on parenting in monogamous prairie voles (Microtus ochrogaster). Developmental Psychobiology, 53(2), 118–131. doi:10.1002/dev.v53.2
2. T.H.Ahern,, M.E.Modi,, J.P.Burkett,, & L.J.Young, (2009). Evaluation of two automated metrics for analyzing partner preference tests. Journal of NeuroscienceMethods, 182(2), 180–188. doi:10.1016/j.jneumeth.2009.06.010
3. T.H.Ahern,, & L.J.Young, (2009). The impact of early life family structure on adult social attachment, alloparental behavior, and the neuropeptide systems regulating affiliative behaviors in the monogamous prairie vole (Microtus ochrogaster). Frontiers in Behavioral Neuroscience, 3, 17. doi:10.3389/neuro.08.017.2009
4. M.J.Bakermans-Kranenburg,, & M.H.Van Ijzendoorn, (2008). Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Social Cognitive and Affective Neuroscience, 3(2), 128–134. doi:10.1093/scan/nsn004
5. K.L.Bales,, E.Boone,, P.Epperson,, G.Hoffman,, & C.S.Carter, (2011). Are behavioral effects of early experience mediated by oxytocin? Frontiers in Psychiatry, 2, 24. doi:10.3389/fpsyt.2011.00024
6. C.E.Barrett,, S.E.Arambula,, & L.J.Young, (in press). The oxytocin system promotes resilience to the effects of neonatal isolation on adult social attachment in female prairie voles. Transl Psychiatry.
7. C.E.Barrett,, A.C.Keebaugh,, T.H.Ahern,, C.E.Bass,, E.F.Terwilliger,, & L.J.Young, (2013). Variation in vasopressin receptor (Avpr1a) expression creates diversity in behaviors related to monogamy in prairie voles. Hormones and Behavior, 63(3), 518–526. doi:10.1016/j.yhbeh.2013.01.005
8. C.E.Barrett,, M.E.Modi,, B.C.Zhang,, H.Walum,, K.Inoue,, & L.J.Young, (2014). Neonatal melanocortin receptor agonist treatment reduces play fighting and promotes adult attachment in prairie voles in a sex-dependent manner. Neuropharmacology, 85, 357–366. doi:10.1016/j.neuropharm.2014.05.041
9. O.J.Bosch,, S.L.Meddle,, D.I.Beiderbeck,, A.J.Douglas,, & I.D.Neumann, (2005). Brain oxytocin correlates with maternal aggression: Link to anxiety. Journal of Neuroscience, 25(29), 6807–6815. doi:10.1523/JNEUROSCI.1342-05.2005
10. B.Bradley,, D.Westen,, K.B.Mercer,, E.B.Binder,, T.Jovanovic,, & D.Crain,, … C.Heim, (2011). Association between childhood maltreatment and adult emotional dysregulation in a low-income, urban, African American sample: Moderation by oxytocin receptor gene. Development and Psychopathology, 23(2), 439–452. doi:10.1017/S0954579411000162
11. P.Burbach,, L.J.Young,, & J.Russell, (2006). Oxytocin: Synthesis, secretion and reproductive functions. In J.D.Neill (Ed.), Knobil an Neill’s physiology of reproduction (pp. 3055–3127). New York, NY: Elsevier.
12. J.P.Burkett,, L.L.Spiegel,, K.Inoue,, A.Z.Murphy,, & L.J.Young, (2011). Activation of μ-opioid receptors in the dorsal striatum is necessary for adult social attachment in monogamous prairie voles. Neuropsychopharmacology, 36(11), 2200–2210. doi:10.1038/npp.2011.117
13. D.B.Campbell,, D.Datta,, S.T.Jones,, E.Batey Lee,, J.S.Sutcliffe,, E.A.D.Hammock,, & P.Levitt, (2011). Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder. Journal of Neurodevelopmental Disorders, 3, 101–112. doi:10.1007/s11689-010-9071-2
14. Y.Cao,, R.Wu,, F.Tai,, X.Zhang,, P.Yu,, X.An,, … P.Hao, (2014). Neonatal paternal deprivation impairs social recognition and alters levels of oxytocin and estrogen receptor α mRNA expression in the MeA and NAcc, and serum oxytocin in mandarin voles. Hormones and Behavior, 65(1), 57–65. doi:10.1016/j.yhbeh.2013.11.005
15. C.S.Carter,, J.R.Williams,, D.M.Witt,, & T.R.Insel, (1992). Oxytocin and social bonding. Annals of the New York Academy of Sciences, 652, 204–211. doi:10.1111/nyas.1992.652.issue-1
16. E.Choleris,, A.E.Clipperton-Allen,, A.Phan,, & M.Kavaliers, (2009). Neuroendocrinology of social information processing in rats and mice. Frontiers in Neuroendocrinology, 30, 442–459. doi:10.1016/j.yfrne.2009.05.003
17. E.Choleris,, S.R.Little,, J.A.Mong,, S.V.Puram,, R.Langer,, & D.W.Pfaff, (2007). Microparticle-based delivery of oxytocin receptor antisense DNA in the medial amygdala blocks social recognition in female mice. Proceedings of the National Academy of Sciences, 104(11), 4670–4675. doi:10.1073/pnas.0700670104
18. Z.R.Donaldson,, L.Spiegel,, & L.J.Young, (2010). Central vasopressin V1a receptor activation is independently necessary for both partner preference formation and expression in socially monogamous male prairie voles. Behavioral Neuroscience, 124(1), 159–163. doi:10.1037/a0018094
19. J.N.Ferguson,, J.M.Aldag,, T.R.Insel,, & L.J.Young, (2001). Oxytocin in the medial amygdala is essential for social recognition in the mouse. The Journal of Neuroscience, 21(20), 8278–8285.
20. J.N.Ferguson,, L.J.Young,, E.F.Hearn,, M.M.Matzuk,, T.R.Insel,, & J.T.Winslow, (2000). Social amnesia in mice lacking the oxytocin gene. Nature Genetics, 25(3), 284–288. doi:10.1038/77040
21. S.G.Gregory,, J.J.Connelly,, A.J.Towers,, J.Johnson,, D.Biscocho,, C.A.Markunas,, … M.A.Pericak-Vance, (2009). Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Medicine, 7, 62.
22. T.R.Insel,, & L.E.Shapiro, (1992). Oxytocin receptor distribution reflects social organization in monogamous and polygamous voles. Proceedings of the National Academy of Sciences, 89(13), 5981–5985. doi:10.1073/pnas.89.13.5981
23. S.Jacob,, C.W.Brune,, C.S.Carter,, B.L.Leventhal,, C.Lord,, & E.H.CookJr., (2007). Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neuroscience Letters, 417(1), 6–9. doi:10.1016/j.neulet.2007.02.001
24. Z.V.Johnson,, & L.J.Young, (2015). Neurobiological mechanisms of social attachment and pair bonding. Current Opinion in Behavioral Sciences, 3, 38–44. doi:10.1016/j.cobeha.2015.01.009
25. A.C.Keebaugh,, & L.J.Young, (2011). Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults. Hormones and Behavior, 60(5), 498–504. doi:10.1016/j.yhbeh.2011.07.018
26. E.Lerer,, S.Levi,, S.Salomon,, A.Darvasi,, N.Yirmiya,, & R.P.Ebstein, (2008). Association between the oxytocin receptor (OXTR) gene and autism: Relationship to Vineland Adaptive Behavior Scales and cognition. Molecular Psychiatry, 13(10), 980–988. doi:10.1038/sj.mp.4002087
27. M.M.Lim,, A.Z.Murphy,, & L.J.Young, (2004). Ventral striatopallidal oxytocin and vasopressin V1a receptors in the monogamous prairie vole (Microtus ochrogaster). The Journal of Comparative Neurology, 468(4), 555–570. doi:10.1002/(ISSN)1096-9861
28. M.M.Lim,, & L.J.Young, (2004). Vasopressin-dependent neural circuits underlying pair bond formation in the monogamous prairie vole. Neuroscience, 125(1), 35–45. doi:10.1016/j.neuroscience.2003.12.008
29. X.Liu,, Y.Kawamura,, T.Shimada,, T.Otowa,, S.Koishi,, T.Sugiyama,, … T.Sasaki, (2010). Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population. Journal of Human Genetics, 55(3), 137–141. doi:10.1038/jhg.2009.140
30. D.LoParo,, & I.D.Waldman, (2014). The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: A meta-analysis. Molecular Psychiatry. Advance online publication. doi:10.1038/mp.2014.77
31. M.Manning,, S.Stoev,, B.Chini,, T.Durroux,, B.Mouillac,, & G.Guillon, (2008). Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: Research tools and potential therapeutic agents. Progress in Brain Research, 170, 473–512.
32. L.A.McGraw,, & L.J.Young, (2010). The prairie vole: An emerging model organism for understanding the social brain. Trends in Neurosciences, 33(2), 103–109. doi:10.1016/j.tins.2009.11.006
33. V.Mileva-Seitz,, M.Steiner,, L.Atkinson,, M.J.Meaney,, R.Levitan,, J.L.Kennedy,, … A.S.Fleming, (2013). Interaction between oxytocin genotypes and early experience predicts quality of mothering and postpartum mood. PLoS One, 8(4), e61443.
34. M.E.Modi,, & L.J.Young, (2011). D-Cycloserine facilitates socially reinforced learning in an animal model relevant to autism spectrum disorders. BiologicalPsychiatry, 70, 298–304. doi:10.1016/j.biopsych.2011.01.026
35. M.E.Modi,, & L.J.Young, (2012). The oxytocin system in drug discovery for autism: Animal models and novel therapeutic strategies. Hormones and Behavior, 61(3), 340–350. doi:10.1016/j.yhbeh.2011.12.010
36. D.E.Olazábal,, & L.J.Young, (2005). Variability in “spontaneous” maternal behavior is associated with anxiety-like behavior and affiliation in Naïve juvenile and adult female prairie voles (Microtus ochrogaster). Developmental Psychobiology, 47(2), 166–178. doi:10.1002/(ISSN)1098-2302
37. D.E.Olazábal,, & L.J.Young, (2006a). Oxytocin receptors in the nucleus accumbens facilitate “spontaneous” maternal behavior in adult female prairie voles. Neuroscience, 141(2), 559–568. doi:10.1016/j.neuroscience.2006.04.017
38. D.E.Olazábal,, & L.J.Young, (2006b). Species and individual differences in juvenile female alloparental care are associated with oxytocin receptor density in the striatum and the lateral septum. Hormones and Behavior, 49(5), 681–687. doi:10.1016/j.yhbeh.2005.12.010
39. A.G.Ophir,, A.Gessel,, D.-J.Zheng,, & S.M.Phelps, (2012). Oxytocin receptor density is associated with male mating tactics and social monogamy. Hormones and Behavior, 61(3), 445–453. doi:10.1016/j.yhbeh.2012.01.007
40. K.J.Parker,, J.P.Garner,, R.A.Libove,, S.A.Hyde,, K.B.Hornbeak,, D.S.Carson,, … A.Y.Hardan, (2014). Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder. Proceedings of the National Academy of Sciences, 111(33), 12258–12263. doi:10.1073/pnas.1402236111
41. S.L.Resendez,, M.Dome,, G.Gormley,, D.Franco,, N.Nevarez,, A.A.Hamid,, & B.T.Aragona, (2013). mu-Opioid receptors within subregions of the striatum mediate pair bond formation through parallel yet distinct reward mechanisms. Journal of Neuroscience, 33(21), 9140–9149. doi:10.1523/JNEUROSCI.4123-12.2013
42. M.M.Riem,, S.Pieper,, D.Out,, M.J.Bakermans-Kranenburg,, & M.H.Van Ijzendoorn, (2010). Oxytocin receptor gene and depressive symptoms associated with physiological reactivity to infant crying. Social Cognitive and Affective Neuroscience, 6(3), 294–300. doi:10.1093/scan/nsq035
43. J.K.Rilling,, & L.J.Young, (2014). The biology of mammalian parenting and its effect on offspring social development. Science, 345(6198), 771–776. doi:10.1126/science.1252723
44. S.M.Rodrigues,, L.R.Saslow,, N.Garcia,, O.P.John,, & D.Keltner, (2009). Oxytocin receptor genetic variation relates to empathy and stress reactivity in humans. Proceedings of the National Academy of Sciences, 106(50), 21437–21441. doi:10.1073/pnas.0909579106
45. H.E.Ross,, S.M.Freeman,, L.L.Spiegel,, X.Ren,, E.F.Terwilliger,, & L.J.Young, (2009). Variation in oxytocin receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles. Journal of Neuroscience, 29(5), 1312–1318. doi:10.1523/JNEUROSCI.5039-08.2009
46. H.E.Ross,, & L.J.Young, (2009). Oxytocin and the neural mechanisms regulating social cognition and affiliative behavior. Frontiers in Neuroendocrinology, 30(4), 534–547. doi:10.1016/j.yfrne.2009.05.004
47. D.Scheele,, N.Striepens,, O.Gunturkun,, S.Deutschlander,, W.Maier,, K.M.Kendrick,, & R.Hurlemann, (2012). Oxytocin modulates social distance between males and females. Journal of Neuroscience, 32(46), 16074–16079. doi:10.1523/JNEUROSCI.2755-12.2012
48. D.Scheele,, A.Wille,, K.M.Kendrick,, B.Stoffel-Wagner,, B.Becker,, O.Gunturkun,, … R.Hurlemann, (2013). Oxytocin enhances brain reward system responses in men viewing the face of their female partner. Proceedings of the National Academy of Sciences, 110(50), 20308–20313. doi:10.1073/pnas.1314190110
49. D.H.Skuse,, A.Lori,, J.F.Cubells,, I.Lee,, K.N.Conneely,, K.Puura,, … L.J.Young, (2014). Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. Proceedings of the National Academy of Sciences of the United States of America, 111(5), 1987–1992. doi:10.1073/pnas.1302985111
50. H.Walum,, P.Lichtenstein,, J.M.Neiderhiser,, D.Reiss,, J.M.Ganiban,, E.L.Spotts,, … L.Westberg, (2012). Variation in the oxytocin receptor gene is associated with pair-bonding and social behavior. BiologicalPsychiatry, 71(5), 419–426. doi:10.1016/j.biopsych.2011.09.002
51. O.Weisman,, O.Zagoory-Sharon,, & R.Feldman, (2012). Oxytocin administration to parent enhances infant physiological and behavioral readiness for social engagement. BiologicalPsychiatry, 72(12), 982–989. doi:10.1016/j.biopsych.2012.06.011
52. A.K.Wermter,, I.Kamp-Becker,, P.Hesse,, G.Schulte-Korne,, K.Strauch,, & H.Remschmidt, (2010). Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics, 153B(2), 629–639.
53. J.R.Williams,, C.S.Carter,, & T.Insel, (1992). Partner preference development in Female prairie voles is facilitated by mating or the central infusion of oxytocin. Annals of the New York Academy of Sciences, 652, 487–489. doi:10.1111/nyas.1992.652.issue-1
54. J.T.Winslow,, N.Hastings,, C.S.Carter,, C.R.Harbaugh,, & T.R.Insel, (1993). A role for central vasopressin in pair bonding in monogamous prairie voles. Nature, 365(6446), 545–548. doi:10.1038/365545a0
55. S.Wu,, M.Jia,, Y.Ruan,, J.Liu,, Y.Guo,, M.Shuang,, … D.Zhang, (2005). Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. BiologicalPsychiatry, 58(1), 74–77. doi:10.1016/j.biopsych.2005.03.013
56. T.Ylisaukko-oja,, M.Alarcón,, R.M.Cantor,, M.Auranen,, R.Vanhala,, E.Kempas,, … L.Peltonen, (2006). Search for autism loci by combined analysis of autism genetic resource exchange and Finnish families. Annals of Neurology, 59(1), 145–155. doi:10.1002/(ISSN)1531-8249
57. L.J.Young, (2001). Oxytocin and vasopressin as candidate genes for psychiatric disorders: Lessons from animal models. American Journal of Medical Genetics, 105(1), 53–54. doi:10.1002/(ISSN)1096-8628
58. L.J.Young, (2015). Oxytocin, social cognition and psychiatry. Neuropsychopharmacology, 40(1), 243–244. doi:10.1038/npp.2014.186
59. L.J.Young,, M.M.Lim,, B.Gingrich,, & T.R.Insel, (2001). Cellular mechanisms of social attachment. Hormones and Behavior, 40(2), 133–138. doi:10.1006/hbeh.2001.1691
60. L.J.Young,, & Z.Wang, (2004). The neurobiology of pair bonding. Nature Neuroscience, 7(10), 1048–1054. doi:10.1038/nn1327
61. C.M.Yrigollen,, S.S.Han,, A.Kochetkova,, T.Babitz,, J.T.Chang,, F.R.Volkmar,, … E.L.Grigorenko, (2008). Genes controlling affiliative behavior as candidate genes for autism. BiologicalPsychiatry, 63(10), 911–916. doi:10.1016/j.biopsych.2007.11.015