1932

Abstract

In the present review, we discuss how the evolution of oxytocin and vasopressin from a single ancestor peptide after gene duplication has stimulated the development of the vertebrate social brain. Separate production sites became possible with a hypothalamic development, which, interestingly, is triggered by the same transcription factors that underlie the development of various subcortical regions where vasopressin and oxytocin receptors are adjacently expressed and which are connected by inhibitory circuits. The opposite modulation of their output by vasopressin and oxytocin could thus create a dynamic equilibrium for rapid responsiveness to external stimuli. At the level of the individual, nurturing early in life can long-lastingly program oxytocin signaling, maintaining a capability of learning and sensitivity to external stimuli that contributes to development of social behavior in adulthood. Oxytocin and vasopressin are thus important for the development of a vertebrate brain that supports bonding between individuals and building of an interactive community.

Loading

Article metrics loading...

/content/journals/10.1146/annurev-neuro-071714-033904
2015-07-08
2024-06-19
Loading full text...

Full text loading...

/deliver/fulltext/neuro/38/1/annurev-neuro-071714-033904.html?itemId=/content/journals/10.1146/annurev-neuro-071714-033904&mimeType=html&fmt=ahah

Literature Cited

  1. Acampora D, Postiglione MP, Avantaggiato V, Di Bonito M, Vaccarino FM. et al. 1999. Progressive impairment of developing neuroendocrine cell lineages in the hypothalamus of mice lacking the Orthopedia gene. Genes Dev. 13:2787–800 [Google Scholar]
  2. Albizu L, Cottet M, Kralikova M, Stoev S, Seyer R. et al. 2010. Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat. Chem. Biol. 6:587–94 [Google Scholar]
  3. Alheid GF, Heimer L. 1988. New perspectives in basal forebrain organization of special relevance for neuropsychiatric disorders: the striatopallidal, amygdaloid, and corticopetal components of substantia innominata. Neuroscience 27:1–39 [Google Scholar]
  4. Auyeung B, Ahluwalia J, Thomson L, Taylor K, Hackett G. et al. 2012. Prenatal versus postnatal sex steroid hormone effects on autistic traits in children at 18 to 24 months of age. Mol. Autism 3:17 [Google Scholar]
  5. Bale TL, Dorsa DM, Johnston CA. 1995. Oxytocin receptor mRNA expression in the ventromedial hypothal-amus during the estrous cycle. J. Neurosci. 15:7 Pt. 15058–64 [Google Scholar]
  6. Bales KL, Carter CS. 2003. Developmental exposure to oxytocin facilitates partner preferences in male prairie voles (Microtus ochrogaster). Behav. Neurosci. 117:854–59 [Google Scholar]
  7. Barberini CL, Morrison SE, Saez A, Lau B, Salzman CD. 2012. Complexity and competition in appetitive and aversive neural circuits. Front. Neurosci. 6:170 [Google Scholar]
  8. Bardet SM, Martinez-de-la-Torre M, Northcutt RG, Rubenstein JL, Puelles L. 2008. Conserved pattern of OTP-positive cells in the paraventricular nucleus and other hypothalamic sites of tetrapods. Brain Res. Bull. 75:231–35 [Google Scholar]
  9. Baron-Cohen S. 2002. The extreme male brain theory of autism. Trends Cogn. Sci. 6:248–54 [Google Scholar]
  10. Bos K, Zeanah CH, Fox NA, Drury SS, McLaughlin KA, Nelson CA. 2011. Psychiatric outcomes in young children with a history of institutionalization. Harv. Rev. Psychiatry 19:115–24 [Google Scholar]
  11. Bosch OJ, Neumann ID. 2012. Both oxytocin and vasopressin are mediators of maternal care and aggression in rodents: from central release to sites of action. Horm. Behav. 61:3293–303 [Google Scholar]
  12. Boudaba C, Tasker JG. 2006. Intranuclear coupling of hypothalamic magnocellular nuclei by glutamate synaptic circuits. Am. J. Physiol. Regul. Integr. Comp. Physiol. 291:1R102–11 [Google Scholar]
  13. Bourgognon J-M, Schiavon E, Salah-Uddin H, Skrzypiec AE, Attwood BK. et al. 2013. Regulation of neuronal plasticity and fear by a dynamic change in PAR1–G protein coupling in the amygdala. Mol. Psychiatry 18:1136–45 [Google Scholar]
  14. Bupesh M, Abellán A, Medina L. 2011. Genetic and experimental evidence supports the continuum of the central extended amygdala and a multiple embryonic origin of its principal neurons. J. Comp. Neurol. 519:3507–31 [Google Scholar]
  15. Busnelli M, Saulière A, Manning M, Bouvier M, Galés C, Chini B. 2012. Functional selective oxytocin-derived agonists discriminate between individual G protein family subtypes. J. Biol. Chem. 287:3617–29 [Google Scholar]
  16. Calabresi P, Picconi B, Tozzi A, Ghiglieri V, Di Filippo M. 2014. Direct and indirect pathways of basal ganglia: a critical reappraisal. Nat. Neurosci. 17:81022–30 [Google Scholar]
  17. Carter CS. 2007. Sex differences in oxytocin and vasopressin: implications for autism spectrum disorders?. Behav. Brain Res. 176:1170–86 [Google Scholar]
  18. Champagne F, Diorio J, Sharma S, Meaney MJ. 2001. Naturally occurring variations in maternal behavior in the rat are associated with differences in estrogen-inducible central oxytocin receptors. PNAS 98:12736–41 [Google Scholar]
  19. Champagne FA, Francis DD, Mar A, Meaney MJ. 2003. Variations in maternal care in the rat as a mediating influence for the effects of environment on development. Physiol. Behav. 79:359–71 [Google Scholar]
  20. Champagne FA, Weaver IC, Diorio J, Dymov S, Szyf M, Meaney MJ. 2006. Maternal care associated with methylation of the estrogen receptor-α1b promoter and estrogen receptor-α expression in the medial preoptic area of female offspring. Endocrinology 147:2909–15 [Google Scholar]
  21. Ciocchi S, Herry C, Grenier F, Wolff SB, Letzkus JJ. et al. 2010. Encoding of conditioned fear in central amygdala inhibitory circuits. Nature 468:277–82 [Google Scholar]
  22. Cottet M, Albizu L, Perkovska S, Jean-Alphonse F, Rahmeh R. et al. 2010. Past, present and future of vasopressin and oxytocin receptor oligomers, prototypical GPCR models to study dimerization processes. Curr. Opin. Pharmacol. 10:59–66 [Google Scholar]
  23. Davis M, Walker DL, Miles L, Grillon C. 2010. Phasic versus sustained fear in rats and humans: role of the extended amygdala in fear versus anxiety. Neuropsychopharmacology 35:1105–35 [Google Scholar]
  24. de Vries GJ, al-Shamma HA. 1990. Sex differences in hormonal responses of vasopressin pathways in the rat brain. J. Neurobiol. 21:5686–93 [Google Scholar]
  25. Devost D, Zingg HH. 2003. Identification of dimeric and oligomeric complexes of the human oxytocin receptor by co-immunoprecipitation and bioluminescence resonance energy transfer. J. Mol. Endocrinol. 31:461–71 [Google Scholar]
  26. Devost D, Zingg HH. 2004. Homo- and hetero-dimeric complex formations of the human oxytocin receptor. J. Neuroendocrinol. 16:372–77 [Google Scholar]
  27. Dölen G, Darvishzadeh A, Huang KW, Malenka RC. 2013. Social reward requires coordinated activity of nucleus accumbens oxytocin and serotonin. Nature 501:7466179–84 [Google Scholar]
  28. Donaldson ZR, Young LJ. 2008. Oxytocin, vasopressin, and the neurogenetics of sociality. Science 322:900–4 [Google Scholar]
  29. Feldman R. 2012. Oxytocin and social affiliation in humans. Horm. Behav. 61:3380–91 [Google Scholar]
  30. Francis D, Diorio J, Liu D, Meaney M. 1999. Nongenomic transmission across generations of maternal behavior and stress responses in the rat. Science 286:1155–58 [Google Scholar]
  31. Gainer H. 2012. Cell-type specific expression of oxytocin and vasopressin genes: an experimental odyssey. J. Neuroendocrinol. 24:4528–38 [Google Scholar]
  32. Gordon I, Vander Wyk BC, Bennett RH, Cordeaux C, Lucas MV. et al. 2013. Oxytocin enhances brain function in children with autism. PNAS 110:5220953–58 [Google Scholar]
  33. Gravati M, Busnelli M, Bulgheroni E, Reversi A, Spaiardi P. et al. 2010. Dual modulation of inward rectifier potassium currents in olfactory neuronal cells by promiscuous G protein coupling of the oxytocin receptor. J. Neurochem. 114:1424–35 [Google Scholar]
  34. Gray TS. 1993. Amygdaloid CRF pathways. Role in autonomic, neuroendocrine, and behavioral responses to stress. Ann. N. Y. Acad. Sci. 697:53–60 [Google Scholar]
  35. Gray TS, Magnuson DJ. 1992. Peptide immunoreactive neurons in the amygdala and the bed nucleus of the stria terminalis project to the midbrain central gray in the rat. Peptides 13:3451–60 [Google Scholar]
  36. Gregory SG, Connelly JJ, Towers AJ, Johnson J, Biscocho D. et al. 2009. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 7:62 [Google Scholar]
  37. Griffin GD, Flanagan-Cato LM. 2011. Ovarian hormone action in the hypothalamic ventromedial nucleus: remodelling to regulate reproduction. J. Neuroendocrinol. 23:6465–71 [Google Scholar]
  38. Grotegut CA, Feng L, Mao L, Phillips Heine R, Murtha AP, Rockman HA. 2011. β-Arrestin mediates oxytocin receptor signaling, which regulates uterine contractility and cellular migration. Am. J. Physiol. Endocrinol. Metab. 300:E468–77 [Google Scholar]
  39. Guzzi F, Zanchetta D, Cassoni P, Guzzi V, Francolini M. et al. 2002. Localization of the human oxytocin receptor in caveolin-1 enriched domains turns the receptor-mediated inhibition of cell growth into a proliferative response. Oncogene 21:1658–67 [Google Scholar]
  40. Hammock EA, Levitt P. 2012. Modulation of parvalbumin interneuron number by developmentally transient neocortical vasopressin receptor 1a (V1aR). Neuroscience 222:20–28 [Google Scholar]
  41. Hammock EA. 2015. Developmental perspectives on oxytocin and vasopressin. Neuropsychopharmacology 40:124 [Google Scholar]
  42. Haubensak W, Kunwar PS, Cai H, Ciocchi S, Wall NR. et al. 2010. Genetic dissection of an amygdala microcircuit that gates conditioned fear. Nature 468:270–76 [Google Scholar]
  43. Hautamäki A, Hautamäki L, Neuvonen L, Maliniemi-Piispanen S. 2010. Transmission of attachment across three generations: continuity and reversal. Clin. Child Psychol. Psychiatry 15:347–54 [Google Scholar]
  44. Heinrichs M, Baumgartner T, Kirschbaum C, Ehlert U. 2003. Social support and oxytocin interact to suppress cortisol and subjective responses to psychosocial stress. Biol. Psychiatry 15:1389–98 [Google Scholar]
  45. Henry J, Cornet V, Bernay B, Zatylny-Gaudin C. 2013. Identification and expression of two oxytocin/vasopressin-related peptides in the cuttlefish Sepia officinalis. Peptides 46:159–66 [Google Scholar]
  46. Hensch TK. 2005. Critical period plasticity in local cortical circuits. Nat. Rev. Neurosci. 6:11877–88 [Google Scholar]
  47. Hökfelt T. 1991. Neuropeptides in perspective: the last ten years. Neuron 7:867–79 [Google Scholar]
  48. Honda K, Higuchi T. 2010. Electrical activities of neurones in the dorsomedial hypothalamic nucleus projecting to the supraoptic nucleus during milk-ejection reflex in the rat. J. Reprod. Dev. 56:336–40 [Google Scholar]
  49. Hong W, Kim DW, Anderson DJ. 2014. Antagonistic control of social versus repetitive self-grooming behaviors by separable amygdala neuronal subsets. Cell 158:1348–61 [Google Scholar]
  50. Huber D, Veinante P, Stoop R. 2005. Vasopressin and oxytocin excite distinct neuronal populations in the central amygdala. Science 308:245–48 [Google Scholar]
  51. Jack A, Connelly JJ, Morris JP. 2012. DNA methylation of the oxytocin receptor gene predicts neural response to ambiguous social stimuli. Front. Hum. Neurosci. 6:280 [Google Scholar]
  52. Jacob S, Brune CW, Carter CS, Leventhal BL, Lord C, Cook EH Jr. 2007. Association of the oxytocin receptor gene (OXTR) in Caucasian children and adolescents with autism. Neurosci. Lett. 417:6–9 [Google Scholar]
  53. Jennings JH, Sparta DR, Stamatakis AM, Ung RL, Pleil KE. et al. 2013. Distinct extended amygdala circuits for divergent motivational states. Nature 496:7444224–28 [Google Scholar]
  54. Jensen Peña C, Neugut YD, Champagne FA. 2013. Developmental timing of the effects of maternal care on gene expression and epigenetic regulation of hormone receptor levels in female rats. Endocrinology 154:4340–51 [Google Scholar]
  55. Keebaugh AC, Young LJ. 2011. Increasing oxytocin receptor expression in the nucleus accumbens of pre-pubertal female prairie voles enhances alloparental responsiveness and partner preference formation as adults. Horm. Behav. 60:5498–504 [Google Scholar]
  56. Knobloch HS, Charlet A, Hoffmann LC, Eliava M, Khrulev S. et al. 2012. Evoked axonal oxytocin release in the central amygdala attenuates fear response. Neuron 73:3553–66 [Google Scholar]
  57. Knobloch HS, Grinevich V. 2014. Evolution of oxytocin pathways in the brain of vertebrates. Front. Behav. Neurosci. 8:31 [Google Scholar]
  58. Kravitz AV, Tye LD, Kreitzer AC. 2012. Distinct roles for direct and indirect pathway striatal neurons in reinforcement. Nat. Neurosci. 15:816–18 [Google Scholar]
  59. Lamm C, Decety J, Singer T. 2011. Meta-analytic evidence for common and distinct neural networks associated with directly experienced pain and empathy for pain. NeuroImage 54:32492–502 [Google Scholar]
  60. Lei K, Cushing BS, Musatov S, Ogawa S, Kramer KM. 2010. Estrogen receptor-α in the bed nucleus of the stria terminalis regulates social affiliation in male prairie voles (Microtus ochrogaster). PLOS ONE 5:e8931 [Google Scholar]
  61. Lim MM, Murphy AZ, Young LJ. 2004. Ventral striatopallidal oxytocin and vasopressin V1a receptors in the monogamous prairie vole (Microtus ochrogaster). J. Comp. Neurol. 468:555–70 [Google Scholar]
  62. Liu X, Kawamura Y, Shimada T, Otowa T, Koishi S. et al. 2010. Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population. J. Hum. Genet. 55:137–41 [Google Scholar]
  63. Lorenz K. 1949. Er redete mit dem Vieh, den Vögeln und den Fischen Wien, Austria: Buchgemeinschaft Donaul. [Google Scholar]
  64. Makinodan M, Rosen KM, Ito S, Corfas G. 2012. A critical period for social experience dependent oligodendrocyte maturation and myelination. Science 337:1357–60 [Google Scholar]
  65. McNeilly AS. 2001. Lactational control of reproduction. Reprod. Fertil. Dev. 13:7–8583–90 [Google Scholar]
  66. Medina L, Abellán A, Vicario A, Desfilis E. 2014. Evolutionary and developmental contributions for understanding the organization of the basal ganglia. Brain Behav. Evol. 83:2112–25 [Google Scholar]
  67. Minakata H. 2010. Oxytocin/vasopressin and gonadotropin-releasing hormone from cephalopods to vertebrates. Ann. N. Y. Acad. Sci. 1200:33–42 [Google Scholar]
  68. Modahl C, Green L, Fein D, Morris M, Waterhouse L. et al. 1998. Plasma oxytocin levels in autistic children. Biol. Psychiatry 43:4270–77 [Google Scholar]
  69. Murat B, Devost D, Andrés M, Mion J, Boulay V. et al. 2012. V1b and CRHR1 receptor heterodimerization mediates synergistic biological actions of vasopressin and CRH. Mol. Endocrinol. 26:3502–20 [Google Scholar]
  70. Murgatroyd C, Patchev AV, Wu Y, Micale V, Bockmühl Y. et al. 2009. Dynamic DNA methylation programs persistent adverse effects of early-life stress. Nat. Neurosci. 12:1559–66 [Google Scholar]
  71. Owen SF, Tuncdemir SN, Bader PL, Tirko NN, Fishell G, Tsien RW. 2013. Oxytocin enhances hippocampal spike transmission by modulating fast-spiking interneurons. Nature 500:458–62 [Google Scholar]
  72. Pagani JH, Zhao M, Cui Z, Williams Avram SK, Caruana DA. et al. 2014. Role of the vasopressin 1b receptor in rodent aggressive behavior and synaptic plasticity in hippocampal area CA2. Mol. Psychiatry 20490–99 [Google Scholar]
  73. Peñagarikano O, Lazaro MT, Lu XH, Gordon A, Dong H. et al. 2015. Exogenous and evoked oxytocin restores social behavior in the Cntnap2 mouse model of autism. Sci. Transl. Med. 7:271 [Google Scholar]
  74. Pitkow LJ, Sharer CA, Ren X, Insel TR, Terwilliger EF, Young LJ. 2001. Facilitation of affiliation and pair-bond formation by vasopressin receptor gene transfer into the ventral forebrain of a monogamous vole. J. Neurosci. 21:187392–96 [Google Scholar]
  75. Rembold M, Loosli F, Adams RJ, Wittbrodt J. 2006. Individual cell migration serves as the driving force for optic vesicle evagination. Science 313:1130–34 [Google Scholar]
  76. Reversi A, Rimoldi V, Marrocco T, Cassoni P, Bussolati G. et al. 2005. The oxytocin receptor antagonist atosiban inhibits cell growth via a “biased agonist” mechanism. J. Biol. Chem. 280:16311–18 [Google Scholar]
  77. Rojas-Muñoz A, Dahm R, Nüsslein-Volhard C. 2005. chokh/rx3 specifies the retinal pigment epithelium fate independently of eye morphogenesis. Dev. Biol. 288:348–62 [Google Scholar]
  78. Romero-Fernandez W, Borroto-Escuela DO, Agnati LF, Fuxe K. 2013. Evidence for the existence of dopamine d2-oxytocin receptor heteromers in the ventral and dorsal striatum with facilitatory receptor-receptor interactions. Mol. Psychiatry 18:849–50 [Google Scholar]
  79. Rood BD, Beck SG. 2014. Vasopressin indirectly excites dorsal raphe serotonin neurons through activation of the vasopressin1A receptor. Neuroscience 260:205–16 [Google Scholar]
  80. Ross HE, Cole CD, Smith Y, Neumann ID, Landgraf R. et al. 2009a. Characterization of the oxytocin system regulating affiliative behavior in female prairie voles. Neuroscience 162:4892–903 [Google Scholar]
  81. Ross HE, Freeman SM, Spiegel LL, Ren X, Terwilliger EF, Young LJ. 2009b. Variation in oxytocin receptor density in the nucleus accumbens has differential effects on affiliative behaviors in monogamous and polygamous voles. J. Neurosci. 29:51312–18 [Google Scholar]
  82. Shah BP, Vong L, Olson DP, Koda S, Krashes MJ. et al. 2014. MC4R-expressing glutamatergic neurons in the paraventricular hypothalamus regulate feeding and are synaptically connected to the parabrachial nucleus. PNAS 111:13193–98 [Google Scholar]
  83. Shah PE, Fonagy P, Strathearn L. 2010. Is attachment transmitted across generations? The plot thickens. Clin. Child Psychol. Psychiatry 15:329–45 [Google Scholar]
  84. Smith AS, Wang Z. 2014. Hypothalamic oxytocin mediates social buffering of the stress response. Biol. Psychiatry 76:4281–88 [Google Scholar]
  85. Stevenson EL, Coldwell HK. 2012. The vasopressin 1b receptor and the neural regulation of social behavior. Horm. Behav. 61:277–82 [Google Scholar]
  86. Stoop R. 2012. Neuromodulation by oxytocin and vasopressin. Neuron 76:142–59 [Google Scholar]
  87. Strathearn L, Fonagy P, Amico J, Montague PR. 2009. Adult attachment predicts maternal brain and oxytocin response to infant cues. Neuropsychopharmacology 34:2655–66 [Google Scholar]
  88. Swanson LW. 2000. Cerebral hemisphere regulation of motivated behavior. Brain Res. 886:1–2113–64 [Google Scholar]
  89. Takesian AE, Hensch TK. 2013. Balancing plasticity/stability across brain development. Prog. Brain Res. 207:3–34 [Google Scholar]
  90. Terrillon S, Barberis C, Bouvier M. 2004. Heterodimerization of V1a and V2 vasopressin receptors determines the interaction with β-arrestin and their trafficking patterns. PNAS 101:1548–53 [Google Scholar]
  91. Terrillon S, Durroux T, Mouillac B, Breit A, Ayoub MA. et al. 2003. Oxytocin and vasopressin V1a and V2 receptors form constitutive homo- and heterodimers during biosynthesis. Mol. Endocrinol. 17:677–91 [Google Scholar]
  92. Tessmar-Raible K, Raible F, Christodoulou F, Guy K, Rembold M. et al. 2007. Conserved sensory-neurosecretory cell types in annelid and fish forebrain: insights into hypothalamus evolution. Cell 129:71389–400 [Google Scholar]
  93. Tolson KP, Gemelli T, Gautron L, Elmquist JK, Zinn AR, Kublaoui BM. 2010. Postnatal Sim1 deficiency causes hyperphagic obesity and reduced Mc4r and oxytocin expression. J. Neurosci. 30:103803–12 [Google Scholar]
  94. Toyoizumi T, Miyamoto H, Yazaki-Sugiyama Y, Atapour N, Hensch TK, Miller KD. 2013. A theory of the transition to critical period plasticity: inhibition selectively suppresses spontaneous activity. Neuron 80:151–63 [Google Scholar]
  95. Tyzio R, Nardou R, Ferrari DC, Tsintsadze T, Shahrokhi A. et al. 2014. Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. Science 343:675–79 [Google Scholar]
  96. Veinante P, Freund-Mercier MJ. 1997. Distribution of oxytocin- and vasopressin-binding sites in the rat extended amygdala: a histoautoradiographic study. J. Comp. Neurol. 383:3305–25 [Google Scholar]
  97. Viviani D, Stoop R. 2008. Opposite effects of oxytocin and vasopressin on the emotional expression of the fear response. Prog. Brain Res. 170:207–18 [Google Scholar]
  98. Vrticka P, Vuilleumier P. 2012. Neuroscience of human social interactions and adult attachment style. Front. Hum. Neurosci. 6:212 [Google Scholar]
  99. Wang H, Duclot F, Liu Y, Wang Z, Kabbaj M. 2013. Histone deacetylase inhibitors facilitate partner preference formation in female prairie voles. Nat. Neurosci. 16:919–24 [Google Scholar]
  100. Wells MJ. 1980. Nervous control of the heartbeat in octopus. J. Exp. Biol. 85:1111–28 [Google Scholar]
  101. Woller MJ, Tannenbaum PL, Schultz-Darken NJ, Eshelman BD, Abbott DH. 2010. Pulsatile gonadotropin-releasing hormone release from hypothalamic explants of male marmoset monkeys compared with male rats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 298:R70–78 [Google Scholar]
  102. Wu S, Jia M, Ruan Y, Liu J, Guo Y. et al. 2005. Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biol. Psychiatry 58:74–77 [Google Scholar]
  103. Xu XJ, Shou XJ, Li J, Jia MX, Zhang JS. et al. 2013. Mothers of autistic children: lower plasma levels of oxytocin and Arg-vasopressin and a higher level of testosterone. PLOS ONE 8:9e74849 [Google Scholar]
  104. Yamaguchi Y, Suzuki T, Mizoro Y, Kori H, Okada K. et al. 2013. Mice genetically deficient in vasopressin V1a and V1b receptors are resistant to jet lag. Science 342:615485–90 [Google Scholar]
  105. Yamamoto Y, Cushing BS, Kramer KM, Epperson PD, Hoffman GE, Carter CS. 2004. Neonatal manipulations of oxytocin alter expression of oxytocin and vasopressin immunoreactive cells in the paraventricular nucleus of the hypothalamus in a gender-specific manner. Neuroscience 125:947–55 [Google Scholar]
  106. Yoshida M, Takayanagi Y, Inoue K, Kimura T, Young LJ. et al. 2009. Evidence that oxytocin exerts anxiolytic effects via oxytocin receptor expressed in serotonergic neurons in mice. J. Neurosci. 29:72259–71 [Google Scholar]
  107. Young LJ, Modi M. 2012. Novel therapeutic for use as an adjunct to psychotherapy US Patent No. 14/017,423 [Google Scholar]
  108. Young LJ, Wang Z. 2004. The neurobiology of pair bonding. Nat. Neurosci. 7:1048–54 [Google Scholar]
  109. Young SF, Griffante C, Aguilera G. 2007. Dimerization between vasopressin V1b and corticotropin releasing hormone type 1 receptors. Cell. Mol. Neurobiol. 27:439–61 [Google Scholar]
/content/journals/10.1146/annurev-neuro-071714-033904
Loading
/content/journals/10.1146/annurev-neuro-071714-033904
Loading

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error