The Relationship of Oxytocin and Reelin in the Brain

  • George D. Pappas
  • C. Sue Carter

Oxytocin (OT) is a small (nine amino acid) peptide, synthesized primarily in the paraventricular and supraoptic nuclei of the hypothalamus. Classically associated with functions such as birth and lactation, OT can also influence social behavior, the hypothalamus–pituitary–adrenal (HPA) axis, and may have a role in the regulation of neural development.


Autism Spectrum Disorder Autism Spectrum Disorder Purkinje Cell Dentate Gyrus Prader Willi Syndrome 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Assenza, G., Biamonte, F., Cesa, R., Strata, P., and Keller, F. (2005). Interaction between reelin and estrogens on Purkinje cells during development: A model of cerebellar pathology in autism and related disorders. Soc. Neurosci. Abstr. 251.2.Google Scholar
  2. Bales, K., Pfeifer, L., and Carter, C. S. (2004a). Sex differences and developmental effects of manipu-lations of oxytocin on anxiety and alloparenting in prairie voles. Dev. Psychobiol. 44:123-131.CrossRefPubMedGoogle Scholar
  3. Bales, K. L., Kim, A. J., Lewis-Reese, A. D., and Carter, C. S. (2004b). Both oxytocin and vaso-pressin may influence alloparental care in male prairie voles. Horm. Behav. 45:354-361.CrossRefPubMedGoogle Scholar
  4. Bales, K. L., Kramer, K. M., Lewis-Reese, A. D., and Carter, C. S. (2006). Effects of stress on parental care are sexually dimorphic in prairie voles. Physiol. Behav. 87:424-429.CrossRefPubMedGoogle Scholar
  5. Baron-Cohen, S. (2002). The extreme male brain theory of autism. Trends Cogn. Sci. 6:248-254.Google Scholar
  6. Bielsky, I. F., Hu, S. B., and Young, L. J. (2005a). Sexual dimorphism in the vasopressin system: lack of an altered behavioral phenotype in female V1a receptor knockout mice. Behav. Brain Res. 164:132-136.CrossRefPubMedGoogle Scholar
  7. Cameron, J. L. (1991). Metabolic cues for the onset of puberty. Horm. Res. 36:97-103.CrossRefPubMedGoogle Scholar
  8. Carter, C. S. (1998). Neuroendocrine perspectives on social attachment and love. Psychoneuroendocrinology 23:779-818.CrossRefPubMedGoogle Scholar
  9. Carter, C. S. (2003). Developmental consequences of oxytocin. Physiol. Behav. 79:383-397.CrossRefPubMedGoogle Scholar
  10. Chen, Y., Sharma, R., Costa, R. H., Costa, E., and Grayson, D. R. (2002). On the epigenetic regu-lation of the human reelin promoter. Nucleic Acids Res. 3:2930-2939.CrossRefGoogle Scholar
  11. Cho, M. M., DeVries, A. C., Williams, J. R., and Carter, C. S. (1999). The effects of oxytocin and vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster). Behav. Neurosci. 113:1071-1080.CrossRefPubMedGoogle Scholar
  12. Cook, E. H., Jr., Courchesne, R. Y., Cox, M. J., Lord, C., Gonen, D., Cuter, S. J., Lincon, A., Nix, K., Haas, R., Levethanal, B. L., and Courchesne, E. (1998). Linkage-disequilibrium mapping of autistic disorder, with 15q11-13 markers. Am. J. Hum. Genet. 62:1077-1083.CrossRefPubMedGoogle Scholar
  13. Corbett, B. A., Mendoza, S., Abdullah, M., Wegelin, J. A., and Levine, S. (2006). Cortisol circa-dian rhythms and response to stress in children with autism. Psychoneuroendocrinology 31:59-68CrossRefPubMedGoogle Scholar
  14. Costa, E., Davis, J., Grayson, D. R., Guidotti, A., Pappas, G. D., and Pesold, C. (2001). Dendritic spine hypoplasticity and downregulation of reelin and GABAergic tone in schizophrenia vul-nerability. Neurobiol. Dis. 8:723-742.CrossRefPubMedGoogle Scholar
  15. Dong, E., Agis-Balboa, C., Simonini, M. V., Grayson, D. R., Costa, E., and Guidotti, A. I. (2005). Reelin and glutamic acid decarboxylase67 promoter remodeling in an epigenetic methionine-induced mouse model of schizophrenia. Proc. Natl. Acad. Sci. USA 102: 12578-12583.CrossRefPubMedGoogle Scholar
  16. Fatemi, S. H., Earle, J. A., and McMenomy, T. (2000). Reduction in reelin immunoreactivity in hippocampus of subjects with schizophrenia, bipolar disorder and major depression. Mol. Psychiatry 5:654-663.CrossRefPubMedGoogle Scholar
  17. Fatemi, S. H., Snow, A. V., Stary, J. M., Araghi-Niknam, M., Reutiman, T. J., Lee, S., Brooks, A. I., and Pearce, D. A. (2005). Reelin signaling is impaired in autism. Biol. Psychiatry 57:777-787.CrossRefPubMedGoogle Scholar
  18. Gimpl, G., and Fahrenholz, F. (2001). The oxytocin receptor system: structure, function, and regu-lation. Physiol. Rev. 81:629-683.PubMedGoogle Scholar
  19. Green, L., Fein, D., Modahl, C., Feinstein, C., Waterhouse, L., and Morris, M. (2001). Oxytocin and autistic disorder: Alterations in peptide forms. Biol. Psychiatry 50:609-613.CrossRefPubMedGoogle Scholar
  20. Hadj-Sahraqui, N., Frederic, F., Delhayi-Bouchaud, N., and Mariani, J. (1996). Gender effect on Purkinje cell loss in the cerebellum of the heterozygous reeler mouse. J. Neurosci. 11:45-58.Google Scholar
  21. Hollander, E., Novotny, S., Hanratty, M., Yaffe, R., DeCaria, C. M., Aronwitz, B. R., and Mosovich, S. (2003). Oxytocin infusion reduces repetitive behaviors in adults with autistic and Asperger’s disorders. Neuropsychopharmacology 28:193-198.CrossRefPubMedGoogle Scholar
  22. Impagnatiello, F., Guidotti, A. R., Pesold, C., Dwivedi, Y., Caruncho, H., Pisu, M. G., Uzunov, D. P., Smalheiser, N. R., Davis, J. M., Pandey, G. N., Pappas, G. D., Tueting, P., Sharma, R. P., and Costa, E. (1998). A decrease of reelin expression as a putative vulnerability factor in schizophrenia. Proc. Natl. Acad. Sci. USA 95:15718-15723.CrossRefPubMedGoogle Scholar
  23. Insel, T. R., O’Brien, D. J., and Leckman, J. F. (1999). Oxytocin, vasopressin, and autism: Is there a connection? Biol. Psychiatry 45:145-157.CrossRefPubMedGoogle Scholar
  24. Kimura, T., Saji, F., Nishimori, K., Ogita, K., Nakamura, H., Koyama, M., and Murata, Y. (2003). Molecular regulation of the oxytocin receptor in peripheral organs. J. Mol. Endocrinol. 30:109-115.CrossRefPubMedGoogle Scholar
  25. Leckman, J. F., and Herman, A. E. (2002). Maternal behavior and developmental psychopathol-ogy. Biol. Psychiatry 51:27-43.CrossRefPubMedGoogle Scholar
  26. Liu, W. S., Pappas, G. D., and Carter, C. S. (2005). Oxytocin receptors are reduced in cortical regions in haploinsufficient reeler (+/−) mice. Neurol. Res. 27:339-345.CrossRefPubMedGoogle Scholar
  27. Maes, M., Goossens, F., Lin, A., De Meester, I., Van Gastel, A., and Scharpe, S. (1998). Effects of psychological stress on serum prolyl endopeptidase and dipeptidyl peptidase IV activity in humans: higher serum prolyl endopeptidase activity is related to stress-induced anxiety. Psychoneuroendocrinology 23:485-495.CrossRefPubMedGoogle Scholar
  28. Maes, M., Lin, A. H., Bonaccorso, S., Goossens, F., Van Gastel, A., Pioli, R., Delmeire, L., and Scharpe, S. (1999). Higher serum prolyl endopeptidase activity in patients with post-traumatic stress disorder. J. Affect. Disord. 53:27-34.CrossRefPubMedGoogle Scholar
  29. Maes, M., Monteleone, P., Bencivenga, R., Goossens, F., Maj, M., van West, D., Bosmans, E., and Scharpe, S. (2001). Lower serum activity of prolyl endopeptidase in anorexia and bulimia ner-vosa. Psychoneuroendocrinology 26:17-26.CrossRefPubMedGoogle Scholar
  30. Meaney, M. J., and Szyf, M. (2005). Maternal care as a model for experience-dependent chromatin plasticity? Trends Neurosci. 28:456-463.CrossRefPubMedGoogle Scholar
  31. Michelini, L. C., Marcelo, M. C., Amico, J., and Morris, M. (2003). Oxytocinergic regulation of cardiovascular function: studies in oxytocin-deficient mice. Am. J. Physiol. Heart Circ. Physiol. 284:H2269-H2276.PubMedGoogle Scholar
  32. Mitsui, T., Nomura, S., Itakura, A., and Mizutaini, S. (2004). Role of aminopeptidases in the blood pressure regulation. Biol. Pharmacol. Bull. 27:768-771.CrossRefGoogle Scholar
  33. Miura, N., Shibata, S., and Watanabe, S. (1995). Increase in the septal vasopressin content by prolyl endopeptidase inhibitors in rats. Neurosci. Lett. 196:128-130.CrossRefPubMedGoogle Scholar
  34. Pappas, G. D., Kriho, V., and Pesold, C. (2001). Reelin in the extracellular matrix and dendritic spines of the cortex and hippocampus: a comparison between wild-type and heterozygous reeler mice by immunoelectron microscopy. J. Neurocytol. 30:413-425.CrossRefPubMedGoogle Scholar
  35. Pappas, G. D., Kriho, V., Liu, W. S., Tremolizzo, L., Lugli, G., and Larson, J. (2003). Immunocytochemical localization of reelin in the olfactory bulb of the heterozygous reeler mouse: an animal model for schizophrenia. Neurol. Res. 25:819-830.CrossRefPubMedGoogle Scholar
  36. Porges, S. W. (2001). The polyvagal theory: phylogenetic substrates of a social nervous system. Int. J. Psychophysiol. 42:123-146.CrossRefPubMedGoogle Scholar
  37. Shapiro, L. E., and Insel, T. R. (1990). Infant’s response to social separation reflects adult differ-ences in affiliative behavior: a comparative developmental study in prairie and montane voles. Dev. Psychobiol. 23:375-393.CrossRefPubMedGoogle Scholar
  38. Shi, L., Fatemi, S. H., Sidwell, R. W., and Patterson, P. H. (2003). Maternal influenza infection causes marked behavioral and pharmacological changes in the offspring. J. Neurosci. 23:297-302.PubMedGoogle Scholar
  39. Thompson, R. R., George, K., Walton, J. C., Orr, S. P., and Benson, J. (2006). Sex-specific influ-ences of vasopressin on human social communication. Proc. Natl. Acad. Sci.. USA 103:7889-7894.CrossRefPubMedGoogle Scholar
  40. Tomizawa, K., Iga, N., Lu, Y. F., Moriwaki, A., Matsushita, M., Li, S. T., Miyamoto, O., Itano, T., and Matsui, H. (2003). Oxytocin improves long-lasting spatial memory during motherhood through MAP kinase cascade. Nature Neurosci. 6:384-390.CrossRefPubMedGoogle Scholar
  41. Tribollet, E., Charpak, S., Schmidt, A., Dubois, D. M., and Dreifuss, J. J. (1989). Appearance and transient expression of OT receptors in fetal, infant, peripubertal rat brain studied by autoradi-ography and electrophysiology. J. Neurosci. 9:1764-1773.PubMedGoogle Scholar
  42. Tsujimoto, M., and Hattori, A. (2005). The oxytocinase subfamily of M1 aminopeptidases. Biochim. Biophys. Acta 1751:9-18.PubMedGoogle Scholar
  43. Tueting, P., Doueiri, M. S., Guidotti, A., Davis, J. M., and Costa, E. (2006). Reelin downregulation in mice and psychosis endophenotypes. Neurosci. Biobehav. Rev. 30:1067-1077.CrossRefGoogle Scholar
  44. Uvnas-Moberg, K. (1998). Oxytocin may mediate the benefits of positive social interaction and emotions. Psychoneuroendocrinology 23:819-835.CrossRefPubMedGoogle Scholar
  45. Weaver, I. C., Champagne, F. A., Brown, S. E., Dymov, S., Sharma, S., Meaney, M. J., and Szyf, M. (2006). Reversal of maternal programming of stress responses in adult offspring through methyl supplementation: altering epigenetic marking later in life. J. Neurosci. 25:11045-11054.CrossRefGoogle Scholar
  46. Welch, M. G., and Ruggiero, D. A. (2005). Predicted role of secretin and oxytocin in the treatment of behavioral and developmental disorders: implications for autism. Int. Rev. Neurobiol. 71:273-314.CrossRefPubMedGoogle Scholar
  47. Winslow, J. T. (2005). Neuropeptides and non-human primate social deficits associated with path-ogenic rearing experience. Int. J. Dev. Neurosci. 23:245-251.CrossRefPubMedGoogle Scholar
  48. Yamamoto, Y., Cushing, B. S., Kramer, K. M., Epperson, P. D., Hoffman, G. E., and Carter, C. S. (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 125:947-955.CrossRefPubMedGoogle Scholar
  49. Young, L. J., Pitkow, L. J., and Ferguson, J. N. (2002). Neuropeptides and social behavior: animal models relevant to autism. Mol. Psychiatry 7:S38-S39.CrossRefPubMedGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • George D. Pappas
    • 1
  • C. Sue Carter
    • 1
  1. 1.Department of Psychiatry, Psychiatric Institute, College of MedicineUniversity of Illinois at ChicagoChicago

Personalised recommendations