**12. References**

[1] Goodson, J.L., A.M. Kelly, and M.A. Kingsbury, *Evolving nonapeptide mechanisms of gregariousness and social diversity in birds.* Hormones and Behavior, 2012. 61(3): p. 239-250.

[2] Godwin, J. and R. Thompson, *Nonapeptides and Social Behavior in Fishes.* Hormones and Behavior, 2012. 61(3): p. 230-238.

66 Neuroendocrinology and Behavior

administration methods [219].

needs to include studies of both males and females.

**11. Conclusions** 

**Author details** 

**12. References** 

Benjamin C. Nephew

*North Grafton, MA, USA* 

239-250.

studies of AVP/OXT on learning suggest that there may be additional benefits to focusing translational studies in this area. One animal research topic that may be of particular interest is the developmental role of AVP and OXT. Treatments which only affect social behavior in older children or adults may be effective with other impairments when administered at a younger age. Changes in the brains of autistic children have been observed in children as young as 6 months [218]. Another issue with the current clinical trials of intranasal oxytocin is the level of dosing. There is debate as to how much OXT crosses the blood brain barrier and has central effects. One hypothesis is that developmental AVP manipulation may be able to address the cognitive impairments of autism. While most of the clinical efforts in AVP/OXT and autism are centered on the development of pharmaceutical treatments, environmental changes may also be effective. It is possible that insults during gestation, such as chronic social stress, are affecting the normal development of AVP/OXT mediated cognitive and social pathways. Another potential benefit of an OXT focused therapy may be as an adjunct to behavioral therapies aimed at improving social skills. One of the limitations of the current OXT manipulations is the available administration methods. The prairie vole partner preference model is a valuable tool for the screening of novel OXT treatments and

In summary, increased translation between the animal research and clinical studies in males and females on the social behavior roles of AVP and OXT has the potential to stimulate rapid progress in the development of effective treatments for stress related disorders, including PTSD, depression and anxiety, and addiction, as well as disorders which involve deficits in affiliation, such as autism. These treatments may involve pharmalogical interventions, modifications to current practices, social interventions, or a combination of approaches. Stress paradigms which are ethologically relevant to both animals and humans, such as social stress for studies of depression and addiction, may generate the most useful data. PTSD and postpartum depression are two disorders that may benefit greatly from AVP and OXT focused studies. Given the available literature on the substantial gender differences in the roles of AVP and OXT, continued research on these peptide hormones

*Department of Biomedical Sciences, Tufts University Cummings School of Veterinary Medicine,* 

[1] Goodson, J.L., A.M. Kelly, and M.A. Kingsbury, *Evolving nonapeptide mechanisms of* 

*gregariousness and social diversity in birds.* Hormones and Behavior, 2012. 61(3): p.


[18] Arletti, R., A. Benelli, R. Poggioli, P. Luppi, B. Menozzi, and A. Bertolini, *Aged rats are still responsive to the antidepressant and memory-improving effects of oxytocin.* Neuropeptides, 1995. 29(3): p. 177-182.

Behavioral Roles of Oxytocin and Vasopressin 69

[31] Veenema, A.H., I.D. Neumann, and L. Rainer, *Central vasopressin and oxytocin release:* 

[32] Lonstein, J.S. and S.C. Gammie, *Sensory, hormonal, and neural controls of maternal* 

[33] Consiglio, A.R. and A.B. Lucion, *Lesion of hypothalamic paraventricular nucleus and* 

[34] Ferris, C.F., K.B. Foote, H.M. Meltser, M.G. Plenby, K.L. Smith, and T.R. Insel, *Oxytocin* 

[35] Consiglio, A.R., A. Borsoi, G.A.M. Pereira, and A.B. Lucion, *Effects of oxytocin* 

[37] Bosch, O.J., S.L. Meddle, D.I. Beiderbeck, A.J. Douglas, and I.D. Neumann, *Brain* 

[38] Veenema, A.H., R. Bredewold, and I.D. Neumann, *Opposite effects of maternal separation* 

[40] Lubin, D.A., J.C. Elliot, M.C. Black, and J.M. Johns, *An oxytocin antagonist infused into the* 

[41] Ragnauth, A.K., N. Devidze, V. Moy, K. Finley, A. Goodwillie, L.M. Kow, L.J. Muglia,

[42] Elliot, J.C., D.A. Lubin, C.H. Walker, and J.M. Johns, *Acute cocaine alters oxytocin levels in* 

[43] Johns, J.M., C.J. Nelson, K.E. Meter, D.A. Lubin, C.D. Couch, A. Ayers, and C.H.

261-276.

591-596.

124: p. 439-448.

25(29): p. 6807-6815.

of Sciences, 1997. 807: p. 606-609.

2003. 117(2): p. 195-201.

35(2): p. 127-134.

525-532.

239.

888.

*regulation of complex social behaviours*, in *Progress in Brain Research*. 2008, Elsevier. p.

*aggression in laboratory rodents.* Neuroscience and Biobehav. Rev., 2002. 26: p. 869-

*maternal aggressive behavior in female rats.* Physiology and Behavior, 1996. 59(4): p.

*in the Amygdala Facilitates Maternal Aggression.* Annals of the New York Academy of Sciences, 1992. 652(Oxytocin in Materials, Sexual, and Social Behaviors): p. 456-457.

*microinjected into the central amygdaloid nucleus and bed nucleus of stria terminalis on maternal aggressive behavior in rats.* Physiology & Behavior, 2005. 85(3): p. 354-362. [36] Bosch, O.J., S.A. Kromer, P.J. Brunton, and I.D. Neumann, *Release of Oxytocin in the* 

*hypothalamic paraventricular nucleus, but not central amygdala or lateral septum in lactating residents and virgin intruders during maternal defense.* Neuroscience, 2004.

*Oxytocin Correlates with Maternal Aggression: Link to Anxiety.* J. Neurosci., 2005.

*on intermale and maternal aggression in C57BL/6 mice: Link to hypothalamic vasopressin and oxytocin immunoreactivity.* Psychoneuroendocrinology, 2007. 32(5): p. 437-450. [39] Giovenardi, M., M.J. Padoin, L.P. Cadore, and A.B. Lucion, *Hypothalamic paraventricular* 

*nucleus, oxytocin, and maternal aggression in rats.* Annals of the New York Academy

*central nucleus of the amygdala increases maternal aggressive behavior.* Behav. Neurosci.,

and D.W. Pfaff, *Female oxytocin gene-knockout mice, in a semi-natural environment, display exaggerated aggressive behavior.* Genes, Brain & Behavior, 2005. 4(4): p. 229-

*the medial preoptic area and amygdala in lactating rat dams: implications for cocaineinduced changes in maternal behavior and maternal aggression.* Neuropeptides, 2001.

Walker, *Dose-dependent effects of multiple acute cocaine injections on maternal behavior and aggression in Sprague-Dawley rats.* Developmental Neuroscience, 1998. 20(6): p.


[31] Veenema, A.H., I.D. Neumann, and L. Rainer, *Central vasopressin and oxytocin release: regulation of complex social behaviours*, in *Progress in Brain Research*. 2008, Elsevier. p. 261-276.

68 Neuroendocrinology and Behavior

980.

789.

Neuropeptides, 1995. 29(3): p. 177-182.

Neuropharmacology, 2010. 58(1): p. 69-77.

Neuropsychopharmacology, 2004. 29: p. 483-493.

*depression.* Life Sciences, 1987. 41(14): p. 1725-1730.

[18] Arletti, R., A. Benelli, R. Poggioli, P. Luppi, B. Menozzi, and A. Bertolini, *Aged rats are* 

[19] Arletti, R. and A. Bertolini, *Oxytocin acts as an antidepressant in two animal models of* 

[20] Ring, R.H., L.E. Schechter, S.K. Leonard, J.M. Dwyer, B.J. Platt, R. Graf, S. Grauer, C.

[21] Slattery, D.A. and I.D. Neumann, *Chronic icv oxytocin attenuates the pathological high* 

[22] Grippo, A.J., D. Gerena, J. Huang, N. Kumar, M. Shah, R. Ughreja, and C. Sue Carter,

[23] De Wied, D., *Behavioural Actions of Neurohypophysial Peptides.* Proceedings of the Royal Society of London. Series B. Biological Sciences, 1980. 210(1178): p. 183-194. [24] Bielsky, I.F., S.B. Hu, K.L. Szegda, H. Westphal, and L.J. Young, *Profound impairment in* 

[25] Jin, D., H.-X. Liu, H. Hirai, T. Torashima, T. Nagai, O. Lopatina, N.A. Shnayder, K.

*still responsive to the antidepressant and memory-improving effects of oxytocin.*

Pulicicchio, L. Resnick, Z. Rahman, S.J. Sukoff Rizzo, B. Luo, C.E. Beyer, S.F. Logue, K.L. Marquis, Z.A. Hughes, and S. Rosenzweig-Lipson, *Receptor and behavioral pharmacology of WAY-267464, a non-peptide oxytocin receptor agonist.*

*anxiety state of selectively bred Wistar rats.* Neuropharmacology, 2010. 58(1): p. 56-61.

*Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles.* Psychoneuroendocrinology, 2007. 32(8–10): p. 966-

*social recognition and reduction in anxiety in vasopressin V1a receptor knockout mice.*

Yamada, M. Noda, T. Seike, K. Fujita, S. Takasawa, S. Yokoyama, K. Koizumi, Y. Shiraishi, S. Tanaka, M. Hashii, T. Yoshihara, K. Higashida, M.S. Islam, N. Yamada, K. Hayashi, N. Noguchi, I. Kato, H. Okamoto, A. Matsushima, A. Salmina, T. Munesue, N. Shimizu, S. Mochida, M. Asano, and H. Higashida, *CD38 is critical for social behaviour by regulating oxytocin secretion.* Nature, 2007. 446(7131): p. 41-45. [26] Boccia, M.M., S.R. Kopf, and C.M. Baratti, *Effects of a Single Administration of Oxytocin or* 

*Vasopressin and Their Interactions with Two Selective Receptor Antagonists on Memory Storage in Mice.* Neurobiology of Learning and Memory, 1998. 69(2): p. 136-146. [27] Boccia, M.M. and C.M. Baratti, *Involvement of Central Cholinergic Mechanisms in the Effects* 

*of Oxytocin and an Oxytocin Receptor Antagonist on Retention Performance in Mice.*

*Glucocorticoid-mediated effects of systemic oxytocin upon memory retrieval.*

*partner preference formation in monogamous voles.* Behav. Neurosci., 1995. 109: p. 782-

[28] de Oliveira, L.F., C. Camboim, F. Diehl, A.R. Consiglio, and J.A. Quillfeldt,

[29] Cushing, B. and C.S. Carter, *Peripheral pulses of oxytocin increase partner preferences in* 

[30] Insel, T.R. and T. Hulihan, *A gender-specific mechanism for pair bonding: Oxytocin and* 

Neurobiology of Learning and Memory, 2000. 74(3): p. 217-228.

Neurobiology of Learning and Memory, 2007. 87(1): p. 67-71.

*female, but not male, prairie voles.* Horm. Behav., 2000. 37: p. 49-56.


[44] Johns, J.M., L.R. Noonan, L. Li, and C.A. Pedersen, *Effects of chronic and acute cocaine treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats.* Behav. Neurosci., 1994. 108(1): p. 107-112.

Behavioral Roles of Oxytocin and Vasopressin 71

[59] Neumann, I.D., L. Torner, and A. Wigger, *Brain oxytocin: differential inhibition of* 

[60] McCarthy, M.M., C.H. McDonald, P.J. Brooks, and D. Goldman, *An anxiolytic action of oxytocin is enhanced by estrogen in the mouse.* Physiol Behav, 1996. 60: p. 1209-1215. [61] Caughey, S.D., S.M. Klampfl, V.R. Bishop, J. Pfoertsch, I.D. Neumann, O.J. Bosch, and

[62] Windle, R.J., N. Shanks, S.L. Lightman, and C.D. Ingram, *Central oxytocin administration* 

[63] Piccinelli, M. and G. Wilkinson, *Gender differences in depression.* The British Journal of

[64] Engelmann, M., K. Ebner, C.T. Wotjak, and R. Landgraf, *Endogenous oxytocin is involved* 

[65] Lee, H.-J., H.K. Caldwell, A.H. Macbeth, and W.S. Young Iii, *Behavioural studies using* 

[66] Lévy, F., K.M. Kendrick, J.A. Goode, R. Guevara-Guzman, and E.B. Keverne, *Oxytocin* 

[67] Campbell, A., *Attachment, aggression and affiliation: The role of oxytocin in female social* 

[68] Nephew, B.C. and R.S. Bridges, *Arginine vasopressin V1a receptor antagonist impairs maternal memory in rats.* Physiology & Behavior, 2008. 95(1-2): p. 182-186. [69] Byrnes, E.M. and R.S. Bridges, *Endogenous opioid facilitation of maternal memory in rats.*

[70] D'Cunha, T.M., S.J. King, A.S. Fleming, and F. Lévy, *Oxytocin receptors in the nucleus* 

[71] Kendrick, K.M., *Oxytocin, motherhood and bonding.* Experimental Physiology, 2000. 85: p.

[72] Kosfeld, M., M. Heinrichs, P.J. Zak, U. Fischbacher, and E. Fehr, *Oxytocin increases trust* 

[73] Zak, P.J., R. Kurzban, and W.T. Matzner, *Oxytocin is associated with human* 

[74] Rilling, J.K., A.C. DeMarco, P.D. Hackett, R. Thompson, B. Ditzen, R. Patel, and G.

Pagnoni, *Effects of intranasal oxytocin and vasopressin on cooperative behavior and associated brain activity in men.* Psychoneuroendocrinology, 2012. 37(4): p. 447-461.

*trustworthiness.* Hormones and Behavior, 2005. 48(5): p. 522-527.

*accumbens shell are involved in the consolidation of maternal memory in postpartum rats.*

D.N. Inga and L. Rainer, Editors. 2008, Elsevier. p. 73-77.

*release.* Brain Research, 1995. 669(2): p. 197-206.

*behavior.* Biological Psychology, 2008. 77(1): p. 1-10.

Behavioral Neuroscience, 2000. 114(4): p. 797-804.

Hormones and Behavior, 2011. 59(1): p. 14-21.

*in humans.* Nature, 2005. 435: p. 673-676.

111s-124s.

*lactating rats.* Neuroscience, 2000. 95: p. 567-575.

Neuroendocrinology, 2011. 23(11): p. 1113-1124.

1997. 138: p. 2829-2834.

Psychiatry, 2000. 177(6): p. 486-492.

*neuroendocrine stress responses and anxiety-related behaviour in virgin, pregnant and* 

S.L. Meddle, *Changes in the Intensity of Maternal Aggression and Central Oxytocin and Vasopressin V1a Receptors Across the Peripartum Period in the Rat.* Journal of

*reduces stress-induced corticosterone release and anxiety behavior in rats.* Endocrinology,

*in short-term olfactory memory in female rats.* Behavioral Brain Res., 1998. 90: p. 89-94.

*temporal and spatial inactivation of the oxytocin receptor*, in *Progress in Brain Research*,

*and vasopressin release in the olfactory bulb of parturient ewes: changes with maternal experience and effects on acetylcholine, γ-aminobutyric acid, glutamate and noradrenaline* 


[59] Neumann, I.D., L. Torner, and A. Wigger, *Brain oxytocin: differential inhibition of neuroendocrine stress responses and anxiety-related behaviour in virgin, pregnant and lactating rats.* Neuroscience, 2000. 95: p. 567-575.

70 Neuroendocrinology and Behavior

[44] Johns, J.M., L.R. Noonan, L. Li, and C.A. Pedersen, *Effects of chronic and acute cocaine* 

[45] Nephew, B.C., R.S. Bridges, D.F. Lovelock, and E.M. Byrnes, *Enhanced maternal* 

[46] Pedersen, C.A., J.A. Ascher, Y.L. Monroe, and A.J. Prange, *Oxytocin induces maternal* 

[47] Pedersen, C.A. and A.J. Prange Jr., *Induction of maternal behavior in virgin rats after intracerebroventricular administration of oxytocin.* PNAS, 1979. 76: p. 6661-6665. [48] Bosch, O.J. and I.D. Neumann, *Brain vasopressin is an important regulator of maternal behavior independent of dams' trait anxiety.* PNAS, 2008. 105: p. 17139-17144. [49] Pedersen, C.A., J.D. Caldwell, C. Walker, G. Ayers, and G.A. Mason, *Oxytocin activates* 

[50] van Leengoed, E., E. Kerker, and H.H. Swanson, *Inhibition of post-partum maternal* 

[51] Takayanagi, Y., M. Yoshida, I. Bielsky, H. Ross, M. Kawamata, T. Onaka, T.

[52] Kendrick, K.M., *Neural control of maternal behavior and olfactory recognition of offspring.*

[53] DaCosta, A.P.C., R.G. GuevaraGuzman, S. Ohkura, J.A. Goode, and K.M. Kendrick, *The* 

[54] Champagne, F., J. Diorio, S. Sharma, and M.J. Meaney, *Naturally occurring variations in* 

[55] Francis, D.D., L.J. Young, M.J. Meaney, and T.B. Insel, *Naturally occurring differences in* 

[57] Champagne, F.A. and M.J. Meaney, *Stress During Gestation Alters Postpartum Maternal* 

[58] Olazabal, D.E. and L.J. Young, *Oxytocin receptors in the nucleus accumbens facilitate* 

*receptors: Gender differences.* J. Neuroendocrinology, 2002. 14: p. 349-353. [56] Shahrokh, D.K., T.-Y. Zhang, J. Diorio, A. Gratton, and M.J. Meaney, *Oxytocin-Dopamine* 

*experienced rats.* Behavioral Neuroscience, 2009. 123(5): p. 949-957.

*behavior in virgin female rats.* Science, 1982. 216(4546): p. 648-650.

Behavioral Neuroscience, 1994. 108(6): p. 1163-1171.

*in the sheep.* J Neuroendocrinol, 1996. 8: p. 163-177.

*oxytocin receptors.* PNAS, 2001. 98(22): p. 12736-12741.

Endo., 1987. 112(2): p. 275-282.

USA, 2005. 102: p. 16096 - 16101.

151(5): p. 2276-2286.

177.

2006. 59(12): p. 1227-1235.

Brain Res. Bull., 1997. 44: p. 383-395.

Behav. Neurosci., 1994. 108(1): p. 107-112.

*treatment on the onset of maternal behavior and aggression in Sprague-Dawley rats.*

*aggression and associated changes in neuropeptide gene expression in reproductively* 

*the postpartum onset of rat maternal behavior in the ventral tegmental and preoptic areas.*

*behavior in the rat by injecting an oxytocin antagonist into the cerebral ventricles.* J.

Yanagisawa, T. Kimura, M. Matzuk, L. Young, and K. Nishimori, *Pervasive social deficits, but normal parturition, in oxytocin receptor-deficient mice.* Proc Natl Acad Sci

*role of oxytocin release in the paraventricular nucleus in the control of maternal behaviour* 

*maternal behaivor in the rat are associated with differences in estrogen-inducible central* 

*maternal care are associated with the expression of oxytocin and vasopressin (V1a)* 

*Interactions Mediate Variations in Maternal Behavior in the Rat.* Endocrinology, 2010.

*Care and the Development of the Offspring in a Rodent Model.* Biological Psychiatry,

*/`spontaneous/' maternal behavior in female prairie voles.* Hormones Behav, 2005. 48: p.


[75] Grewen, K.M., S.S. Girdler, J. Amico, and K.C. Light, *Effects of Partner Support on Resting Oxytocin, Cortisol, Norepinephrine, and Blood Pressure Before and After Warm Partner Contact.* Psychosomatic Medicine, 2005. 67(4): p. 531-538.

Behavioral Roles of Oxytocin and Vasopressin 73

[88] Gordon, I., O. Zagoory-Sharon, J.F. Leckman, and R. Feldman, *Oxytocin, cortisol, and triadic family interactions.* Physiology and Behavior, 2010. 101(5): p. 679-684. [89] Gordon, I., O. Zagoory-Sharon, J.F. Leckman, and R. Feldman, *Oxytocin and the development of parenting in humans.* Biol Psychiatry, 2010. 68: p. 377-382. [90] Keverne, E.B. and J.P. Curley, *Vasopressin, oxytocin, and social behavior.* Curr. Opin.

[91] Insel, T.R., *The challenge of translation in social neuroscience: a review of oxytocin,* 

[92] Frasch, A., T. Zetzsche, A. Steiger, and G.F. Jirikowski, *Reduction of plasma oxytocin levels in patients suffering from major depression.* Adv Exp Med Biol, 1995. 395: p. 257-258. [93] Zetzsche, T., A. Frasch, G. Jirikowski, H. Murck, and A. Steiger, *Nocturnal oxytocin* 

[94] Scantamburlo, G., M. Hansenne, S. Fuchs, W. Pitchot, P. Marechal, and C. Pequeux,

[95] Van Londen, L., J.G. Goekoop, G.M. van Kempen, A.C. Frankhuijzen-Sierevogel, V.M.

[96] Purba, J.S., W.J.G. Hoogendijk, M.A. Hofman, and D.F. Swaab, *Increased Number of* 

*Hypothalamus in Depression.* Arch Gen Psychiatry, 1996. 53(2): p. 137-143. [97] Meynen, G., U.A. Unmehopa, M.A. Hofman, D.F. Swaab, and W.J.G. Hoogendijk,

[98] Hurlemann, R., A. Patin, O.A. Onur, M.X. Cohen, T. Baumgartner, S. Metzler, I.

[99] Evans, S., S.S. Shergill, and B.B. Averbeck, *Oxytocin Decreases Aversion to Angry Faces in* 

[100] Pedersen, C.A., *Biological Aspects of Social Bonding and the Roots of Human Violence.* Annals of the New York Academy of Sciences, 2004. 1036(1): p. 106-127. [101] Ditzen, B., M. Schaer, B. Gabriel, G. Bodenmann, U. Ehlert, and M. Heinrichs,

[103] Turner, R.A., M. Altemus, T. Enos, B. Cooper, and T. McGuinness, *Preliminary research* 

*During Couple Conflict.* Biological Psychiatry, 2009. 65(9): p. 728-731.

[102] Taylor, S.E., *Tend and befriend.* Curr Dir Psychol Sci, 2006. 15: p. 273-277.

*Women.* Stress, 2002. 5(4): p. 269-276.

The Journal of Neuroscience, 2010. 30(14): p. 4999-5007.

*secretion is reduced in major depression.* Biological Psychiatry, 1996. 39(7): p. 584-584.

*Plasma oxytocin levels and anxiety in patients with major depression.*

Wiegant, E.A. van der Velde, and D. De Wied, *Plasma levels of arginine vasopressin elevated in patients with major depression.* Neuropsychopharmacology, 1997. 17: p.

*Vasopressin- and Oxytocin-Expressing Neurons in the Paraventricular Nucleus of the* 

*Hypothalamic oxytocin mRNA expression and melancholic depression.* Mol Psychiatry,

Dziobek, J. Gallinat, M. Wagner, W. Maier, and K.M. Kendrick, *Oxytocin Enhances Amygdala-Dependent, Socially Reinforced Learning and Emotional Empathy in Humans.*

*an Associative Learning Task.* Neuropsychopharmacology, 2010. 35(13): p. 2502-2509.

*Intranasal Oxytocin Increases Positive Communication and Reduces Cortisol Levels* 

*on plasma oxytocin in normal cycling women: Investigating emotion and interpersonal distress.* Psychiatry: Interpersonal and Biological Processes, 1999. 62(2): p. 97-113. [104] Turner, R.A., M. Altemus, D.N. Yip, E. Kupferman, D. Fletcher, A. Bostrom, D.M.

Lyons, and J.A. Amico, *Effects of Emotion on Oxytocin, Prolactin, and ACTH in* 

*vasopressin, and affiliative behavior.* Neuron, 2010. 65: p. 768-779.

Psychoneuroendocrinology, 2007. 32: p. 407-410.

Neurobiol., 2004. 14: p. 777-783.

284-292.

2007. 12(2): p. 118-119.


[88] Gordon, I., O. Zagoory-Sharon, J.F. Leckman, and R. Feldman, *Oxytocin, cortisol, and triadic family interactions.* Physiology and Behavior, 2010. 101(5): p. 679-684.

72 Neuroendocrinology and Behavior

277.

[75] Grewen, K.M., S.S. Girdler, J. Amico, and K.C. Light, *Effects of Partner Support on Resting* 

[76] Carmichael, M.S., *Plasma oxytocin increases in the human sexual response.* J. Clin.

[77] Murphy, M.R., J.R. Seckl, S. Burton, S.A. Checkley, and S.L. Lightman, *Changes in* 

[78] Kruger, T., P. Haake, D. Chereath, W. Knapp, O. Janssen, M. Exton, M. Schedlowski,

[79] Modahl, C., L.A. Green, D. Fein, M. Morris, L. Waterhouse, C. Feinstein, and H. Levin,

[80] Gregory, S., J. Connelly, A. Towers, J. Johnson, D. Biscocho, C. Markunas, C. Lintas, R.

[82] Andari, E., J.-R. Duhamel, T. Zalla, E. Herbrecht, M. Leboyer, and A. Sirigu, *Promoting* 

[83] Hollander, E., S. Novotny, M. Hanratty, R. Yaffe, C.M. DeCaria, B.R. Aronowitz, and S.

*Asperger's Disorders.* Neuropsychopharmacology, 2002. 28(1): p. 193-198. [84] Guastella, A.J., S.L. Einfeld, K.M. Gray, N.J. Rinehart, B.J. Tonge, T.J. Lambert, and I.B.

[85] Guastella, A.J., A.L. Howard, M.R. Dadds, P. Mitchell, and D.S. Carson, *A randomized* 

[86] Feldman, R., I. Gordon, I. Schneiderman, O. Weisman, and O. Zagoory-Sharon, *Natural* 

[87] Naber, F., M.H. van Ijzendoorn, P. Deschamps, H. van Engeland, and M.J. Bakermans-

of the National Academy of Sciences, 2010. 107(9): p. 4389-4394.

*Spectrum Disorders.* Biological Psychiatry, 2010. 67(7): p. 692-694.

*disorder.* Psychoneuroendocrinology, 2009. 34(6): p. 917-923.

Psychoneuroendocrinology, 2010. 35(10): p. 1583-1586.

*oxytocin receptor deficiency in autism.* BMC Medicine, 2009. 7(1): p. 62. [81] Sebat, J., B. Lakshmi, D. Malhotra, J. Troge, C. Lese-Martin, T. Walsh, B. Yamrom, S.

*arousal in men.* Journal of Endocrinology, 2003. 177(1): p. 57-64.

*Contact.* Psychosomatic Medicine, 2005. 67(4): p. 531-538.

Endocrinol. Metab., 1987. 64: p. 27-31.

*autism.* Science, 2007. 316: p. 445 - 449.

Metab., 1987. 65: p. 738-741.

*Oxytocin, Cortisol, Norepinephrine, and Blood Pressure Before and After Warm Partner* 

*oxytocin and vasopressin secretion during sexual activity in men.* J. Clin. Endocrinol.

and U. Hartmann, *Specificity of the neuroendocrine response to orgasm during sexual* 

*Plasma oxytocin levels in autistic children.* Biological Psychiatry, 1998. 43(4): p. 270-

Abramson, H. Wright, P. Ellis, C. Langford, G. Worley, G.R. Delong, S. Murphy, M. Cuccaro, A. Persico, and M. Pericak-Vance, *Genomic and epigenetic evidence for* 

Yoon, A. Krasnitz, J. Kendall, A. Leotta, D. Pai, R. Zhang, Y. Lee, J. Hicks, S. Spence, A. Lee, K. Puura, T. Lehtimaki, D. Ledbetter, P. Gregersen, J. Bregman, J. Sutcliffe, V. Jobanputra, W. Chung, D. Warburton, M. King, D. Skuse, D. Geschwind, and T. Gilliam, *Strong association of de novo copy number mutations with* 

*social behavior with oxytocin in high-functioning autism spectrum disorders.* Proceedings

Mosovich, *Oxytocin Infusion Reduces Repetitive Behaviors in Adults with Autistic and* 

Hickie, *Intranasal Oxytocin Improves Emotion Recognition for Youth with Autism* 

*controlled trial of intranasal oxytocin as an adjunct to exposure therapy for social anxiety* 

*variations in maternal and paternal care are associated with systematic changes in oxytocin following parent–infant contact.* Psychoneuroendocrinology, 2010. 35(8): p. 1133-1141.

Kranenburg, *Intranasal oxytocin increases fathers' observed responsiveness during play with their children: A double-blind within-subject experiment.*


[105] Taylor, S.E., S. Saphire-Bernstein, and T.E. Seeman, *Are Plasma Oxytocin in Women and Plasma Vasopressin in Men Biomarkers of Distressed Pair-Bond Relationships?* Psychological Science, 2010. 21(1): p. 3-7.

Behavioral Roles of Oxytocin and Vasopressin 75

[119] Heim, C. and E.B. Binder, *Current research trends in early life stress and depression: Review* 

[120] Heim, C., L.J. Young, D.J. Newport, T. Mletzko, A.H. Miller, and C.B. Nemeroff, *Lower* 

[121] Steube, A.M., K.M. Grewen, C.A. Pedersen, C. Propper, and S. Meltzer-Brody, *Failed* 

[122] Onaka, T., Y. Takayanagi, and M. Yoshida, *Roles of Oxytocin Neurones in the Control of* 

[123] Rimmele, U., K. Hediger, M. Heinrichs, and P. Klaver, *Oxytocin makes a face in memory* 

[124] Wang, Z., C.F. Ferris, and G.J.D. Vries, *Role of Septal Vasopressin Innervation in Paternal* 

[125] Winslow, J., N. Hastings, C.S. Carter, C. Harbaugh, and T.R. Insel, *A role for central* 

[126] Pitkow, L.J., *Facilitation of affiliation and pair-bond formation by vasopressin receptor gene* 

[127] Lim, M.M., *Enhanced partner preference in promiscuous species by manipulating the* 

[128] Lim, M.M. and L.J. Young, *Vasopressin-dependent neural circuits underlying pair bond ormation in the monogamous prairie vole.* Neuroscience, 2004. 125: p. 35-45. [129] Goodson, J.L. and A.H. Bass, *Social behavior functions and related anatomical* 

[130] Ferris, C.F., D.M. Meenan, J.F. Axelson, and H.E. Albers, *A vasopressin antagonist can* 

[131] Ferris, C.F. and M. Potegal, *Vasopressin receptor blockade in the anterior hypothalamus suppresses aggression in hamsters.* Physiol. and Behav., 1988. 44: p. 235-239. [132] Bester-Meredith, J.K., P.A. Martin, and C.A. Marler, *Manipulations of Vasopressin alter* 

[133] Caldwell, H.K. and H.E. Albers, *Effect of photoperiod on vasopressin induced aggression in* 

[134] Gobrogge, K.L., Y. Liu, L.J. Young, and Z. Wang, *Anterior hypothalamic vasopressin* 

Experimental Neurology, 2011. 233(1): p. 102-111.

*mechanism.* J. Women's Health, 2011. 21(3): p. 264-272.

*expression of a single gene.* Nature, 2004. 429: p. 754-757.

*Peromyscus mice.* Aggressive Behavior, 2005. 31: p. 189-199.

*Syrian hamsters.* Horm. and Behav., 2004. 46: p. 444-449.

2008. 14(10): p. 954-958.

2012. 24(4): p. 587-598.

7396.

p. 246-265.

p. 135-138.

*amiliar.* J Neurosci, 2009. 29: p. 38-42.

of Sciences, 1994. 91(1): p. 400-404.

*of human studies on sensitive periods, gene–environment interactions, and epigenetics.*

*CSF oxytocin concentrations in women with a history of childhood abuse.* Mol Psychiatry,

*actation and perinatal depression: Common problems with shared neuroendocrine* 

*Stress, Energy Metabolism, and Social Behaviour.* Journal of Neuroendocrinology,

*Behavior in Prairie Voles (Microtus ochrogaster).* Proceedings of the National Academy

*vasopressin in pair bonding in monogamous prairie voles.* Nature, 1993. 365: p. 545-548.

*transfer into the ventral forebrain of a monogamous vole.* J. Neurosci., 2001. 21: p. 7392-

*characteristics of vasotocin/vasopressin systems in vertebrates.* Brain Res. Rev., 2001. 35:

*reverse dominant/subordinate behavior in hamsters.* Physiology and Behavior, 1986. 38:

*aggression differently across testing conditions in monogamous and non-monogamous* 

*regulates pair-bonding and drug-induced aggression in a monogamous rodent.* Proceedings of the National Academy of Sciences, 2009. 106(45): p. 19144-19149.


[119] Heim, C. and E.B. Binder, *Current research trends in early life stress and depression: Review of human studies on sensitive periods, gene–environment interactions, and epigenetics.* Experimental Neurology, 2011. 233(1): p. 102-111.

74 Neuroendocrinology and Behavior

28: p. 1162-1169.

18: p. 965-970.

273.

2004. 21: p. 1155-1166.

29(8): p. 1541-1564.

2655-2666.

[105] Taylor, S.E., S. Saphire-Bernstein, and T.E. Seeman, *Are Plasma Oxytocin in Women and* 

[106] Nelson, E.E. and J. Panksepp, *Brain substrates of infant-mother attachment: Contributions* 

[107] Levine, A., O. Zagoory-Sharon, R. Feldman, and A. Weller, *Oxytocin during pregnancy* 

[108] Feldman, R., A. Weller, O. Zagoory-Sharon, and A. Levine, *Evidence for a* 

[109] Broad, K.D., J.P. Curley, and E.B. Keverne, *Mother–infant bonding and the evolution of* 

[110] Bartels, A. and S. Zeki, *The neural correlates of maternal and romantic love.* Neuroimage,

[111] Uvnäs-Mobcrg, K., A.-M. Widström, E. Nissen, and H. Björvell, *Personality traits in* 

[112] Bakermans-Kranenburg, M.J. and M.H. van IJzendoorn, *Oxytocin receptor (OXTR) and* 

[113] Bakermans-Kranenburg, M.J., M.H. van Ijzendoorn, M.M.E. Riem, M. Tops, and L.R.A.

[115] Strathearn, L., P. Fonagy, J. Amico, and P.R. Montague, *Adult attachment predicts* 

[116] Skrundz, M., M. Bolten, I. Nast, D.H. Hellhammer, and G. Meinlschmidt, *Plasma* 

[117] Ozsoy, S., E. Esel, and M. Kula, *Serum oxytocin levels in patients with depression and the effects of gender and antidepressant treatment.* Psychiatry Res, 2009. 169: p. 249-252. [118] Cyranowski, J.M., T.L. Hofkens, E. Frank, H. Seltman, H.-M. Cai, and J.A. Amico,

*Depression.* Neuropsychopharmacology, 2011. 36(9): p. 1886-1893.

Psychosomatic Medicine, 2008. 70(9): p. 967-975.

Psychological Science, 2010. 21(1): p. 3-7.

Biological Sciences, 2006. 361(1476): p. 2199-2214.

and Affective Neuroscience, 2008. 3(2): p. 128-134.

*Plasma Vasopressin in Men Biomarkers of Distressed Pair-Bond Relationships?*

*of opioids, oxytocin, and norepinephrine.* Neurosci Biobehav Rev, 1998. 22: p. 437-452.

*and early postpartum: Individual patterns and maternal-fetal attachment.* Peptides, 2007.

*neuroendocrinological foundation of human affiliation: plasma oxytocin levels across pregnancy and the postpartum period predict mother-infant bonding.* Psychol Sci, 2007.

*mammalian social relationships.* Philosophical Transactions of the Royal Society B:

*women 4 days postpartum and their correlation with plasma levels of oxytocin and prolactin.* Journal of Psychosomatic Obstetrics & Gynecology, 1990. 11(4): p. 261-

*serotonin transporter (5-HTT) genes associated with observed parenting.* Social Cognitive

Alink, *Oxytocin decreases handgrip force in reaction to infant crying in females without harsh parenting experiences.* Social Cognitive and Affective Neuroscience, 2011. [114] Light, K.C., K.M. Grewen, J.A. Amico, M. Boccia, K.A. Brownley, and J.M. Johns,

*Deficits in plasma oxytocin responses and increased negative affect, stress, and blood pressure in mothers with cocaine exposure during pregnancy.* Addictive Behaviors, 2004.

*maternal brain and oxytocin response to infant cues.* Neuropsychopharm, 2009. 34: p.

*Oxytocin Concentration during Pregnancy is associated with Development of Postpartum* 

*Evidence of Dysregulated Peripheral Oxytocin Release Among Depressed Women.*


[135] Ferris, C.F., R.H. Melloni, G. Koppel, K.W. Perry, R.W. Fuller, and Y. Delville, *Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive behavior in golden hamsters.* J Neurosci, 1997. 17: p. 4331 - 4340.

Behavioral Roles of Oxytocin and Vasopressin 77

[149] Serradeil-Le Gal, C., J. Wagnon, J. Simiand, G. Griebel, C. Lacour, and G. Guillon,

[150] Serradeil-Le, G.C., S. Derick, G. Brossard, M. Manning, J. Simiand, and R. Gaillard,

[151] Wersinger, S.R., E.I. Ginnns, A.M. O'Carroll, S.J. Lolait, and W.S. Young Iii, *Vasopressin* 

[152] Bosch, O.J., S.A. Kromer, and I.D. Neumann, *Prenatal stress: opposite effects on anxiety* 

*selectively bred for high and low anxiety.* Eur. J. Neurosci., 2006. 23: p. 541-551. [153] Keck, M.E., A. Wigger, T. Welt, M.B. Muller, A. Gesing, and J. Reul, *Vasopressin* 

[154] Wigger, A., M.M. Sanchez, K.C. Mathys, K. Ebner, E. Frank, and D. Liu, *Alterations in* 

[156] Murgatroyd, C., A. Wigger, E. Frank, N. Singewald, M. Bunck, F. Holsboer, R.

[157] Porsolt, R., M. Le Pichon, and M. Jalfre, *Depression: a new animal model sensitive to* 

[158] Wotjak, C.T., J. Ganster, G. Kohl, F. Holsboer, R. Landgraf, and M. Engelmann,

[159] Ebner, K., C.T. Wotjak, F. Holsboer, R. Landgraf, and M. Engelmann, *Vasopressin* 

[160] Ebner, K., C.T. Wotjak, R. Landgraf, and M. Engelmann, *Forced swimming triggers* 

*antidepressant treatments.* Nature, 1977. 266: p. 730-732.

*response in rats.* Eur J Neurosci, 1999. 11: p. 997-1002.

Neuroscience, 1998. 85: p. 1209-1222.

Neurosci, 2002. 15: p. 384-388.

*critical role of vasopressin.* Neuropsychopharmacology, 2004. 29: p. 1-14. [155] Landgraf, R., M.S. Keler, M. Bunck, C. Murgatroyd, D. Spengler, M. Zimbelmann, M.

*receptor antagonist.* J Pharmacol Exp Ther, 2002. 300: p. 1122-1130.

*for the V1b receptor in mammals.* Stress, 2003. 6: p. 199-206.

2002. 7(9): p. 975-984.

26: p. 94-105.

89-102.

24(35): p. 7762-7770.

*Characterization of (2S,4R)-1-[lsqb]5-chloro-1-[lsqb](2,4-dimethoxyphenyl)sulfonyl[rsqb]- 3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl[rsqb]-4-hydroxy-N,N-dimethyl-2 pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b* 

*Functional and pharmacological characterization of the first specific agonist and antagonist* 

*V1b receptor knockout reduces aggressive behavior in male mice.* Molecular Psychiatry,

*and hypothalamic expression of vasopressin and corticotropin releasing hormone in rats* 

*mediates the response of the combined dexamethasone//CRH test in hyper-anxious rats: implications for pathogenesis of affective disorders.* Neuropsychopharmacology, 2002.

*central neuropeptide expression, release, and receptor binding in rats bred for high anxiety:* 

Nubaumer, L. Czibere, C.W. Turck, N. Singewald, D. Rujescu, and E. Frank, *Candidate genes of anxiety-related behavior in HAB/LAB rats and mice: Focus on vasopressin and glyoxalase-I.* Neuroscience & Biobehavioral Reviews, 2007. 31(1): p.

Landgraf, and D. Spengler, *Impaired repression at a vasopressin promoter polymorphism underlies overexpression of vasopressin in a rat model of trait anxiety.* J. Neurosci., 2004.

*Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: New insights into the secretory capacities of peptidergic neurons.*

*released within the septal brain area during swim stress modulates the behavioral stress* 

*vasopressin release within the amygdala to modulate stress-coping strategies in rats.* Eur J


[149] Serradeil-Le Gal, C., J. Wagnon, J. Simiand, G. Griebel, C. Lacour, and G. Guillon, *Characterization of (2S,4R)-1-[lsqb]5-chloro-1-[lsqb](2,4-dimethoxyphenyl)sulfonyl[rsqb]- 3-(2-methoxy-phenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl[rsqb]-4-hydroxy-N,N-dimethyl-2 pyrrolidine carboxamide (SSR149415), a selective and orally active vasopressin V1b receptor antagonist.* J Pharmacol Exp Ther, 2002. 300: p. 1122-1130.

76 Neuroendocrinology and Behavior

1074: p. 425-430.

2001. 39: p. 285-294.

85: p. 125s-130s.

2007. 178(1): p. 123-127.

808.

[135] Ferris, C.F., R.H. Melloni, G. Koppel, K.W. Perry, R.W. Fuller, and Y. Delville,

[136] Albers, E.H., A. Dean, M.C. Karom, D. Smith, and K.L. Huhman, *Role of V1a vasopressin* 

[137] Ferris, C.F., S. Lu, T. Messenger, C.D. Guillon, N. Heindel, M. Miller, G. Koppel, F.R.

*pubertal Syrian hamsters.* Hormones and Behavior, 2010. 58(1): p. 177-191. [139] Carter, C.S., E.M. Boone, H. Pounajafi-Nazarloo, and K.L. Bales, *Consequences of early* 

[140] Parker, K.J. and T.M. Lee, *Central vasopressin administration regulates the onset of* 

[141] Bester-Meredith, J.K., L.J. Young, and C.A. Marler, *Species differences in paternal behavior* 

[142] Bester-Meredith, J.K. and C.A. Marler, *The Association between male offspring aggression* 

[143] Liebsch, G., C.T. Wotjak, R. Landgraf, and M. Engelmann, *Septal vasopressin modulates* 

[144] Englemann, M., C.T. Wotjak, K. Ebner, and R. Landgraf, *Behavioural impact of* 

[145] Appenrodt, E., R. Schnabel, and H. Schwarzberg, *Vasopressin administration modulates anxiety-related behavior in rats.* Physiology & Behavior, 1998. 64(4): p. 543-547. [146] Egashira, N., A. Tanoue, T. Matsuda, E. Koushi, S. Harada, Y. Takano, G. Tsujimoto, K.

[147] Caldwell, H. and W. Young, *Oxytocin and vasopressin: genetics and behavioral* 

[148] Griebel, G., J. Simiand, C.S.L. Gal, J. Wagnon, M. Pascal, and B. Scatton, *Anxiolytic- and* 

Neuroactive Proteins and Peptides, 2006(3): p. 573-607.

Proc Natl Acad Sci USA, 2002. 99: p. 6370-6375.

*anxiety-related behaviour in rats.* Neurosci Lett, 1996. 217: p. 101-104.

Developmental Neurosci., 2009. 31(4): p. 25-37.

*and receptors.* Hormones and Behavior, 1999. 36: p. 25-38.

*behavior in golden hamsters.* J Neurosci, 1997. 17: p. 4331 - 4340.

*Vasopressin/serotonin interactions in the anterior hypothalamus control aggressive* 

*receptors in the control of aggression in Syrian hamsters.* Brain Research, 2006. 1073-

Bruns, and N.G. Simon, *Orally active vasopressin V1a receptor antagonist, SRX251, selectively blocks aggressive behavior.* Pharm. Biochem. Behav., 2006. 83: p. 169-174. [138] Melloni Jr, R.H. and L.A. Ricci, *Adolescent exposure to anabolic/androgenic steroids and the* 

*neurobiology of offensive aggression: A hypothalamic neural model based on findings in* 

*experiences and exposure to oxytocin and vasopressin are sexuallly dimorphic.*

*acultative paternal behavior in Microtus pennsylvanicus (Meadow voles).* Horm. Behav.,

*and aggression in Peromyscus and their associations with vasopressin immunoreactivity* 

*and paternal and maternal behavior of Peromyscus mice.* Ethology, 2003. 109(10): p. 797-

*ntraseptally released vasopressin and oxytocin in rats.* Experimental Physiology, 2000.

Mishima, K. Iwasaki, and M. Fujiwara, *Impaired social interaction and reduced anxietyrelated behavior in vasopressin V1a receptor knockout mice.* Behavioural Brain Research,

*implications.* Handbook of Neurochemistry and Molecular Neurobiology

*antidepressant-like effects of the non-peptide vasopressin V-1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders.*


[161] Salomé, N., J. Stemmelin, C. Cohen, and G. Griebel, *Differential roles of amygdaloid nuclei n the anxiolytic- and antidepressant-like effects of the V1b receptor antagonist, SSR149415, in rats.* Psychopharmacology, 2006. 187(2): p. 237-244.

Behavioral Roles of Oxytocin and Vasopressin 79

[176] Kessler, M.S., O.J. Bosch, M. Bunck, R. Landgraf, and I.D. Neumann, *Maternal care* 

[177] Curley, J.P., C.L. Jensen, B. Franks, and F.A. Champagne, *Variation in maternal and* 

[178] Wersinger, S.R., J.L. Temple, H.K. Caldwell, and W.S. Young, *Inactivation of the* 

[179] Guastella, A.J., A.R. Kenyon, G.A. Alvares, D.S. Carson, and I.B. Hickie, *Intranasal* 

[180] Guastella, A.J., A.R. Kenyon, C. Unkelbach, G.A. Alvares, and I.B. Hickie, *Arginine* 

[181] Thompson, R.R., K. George, J.C. Walton, S.P. Orr, and J. Benson, *Sex-specific influences of vasopressin on human social communication.* PNAS, 2006. 103(20): p. 7889-7894. [182] Thompson, R., S. Gupta, K. Miller, S. Mills, and S. Orr, *The effects of vasopressin on* 

[183] Coccaro, E.F., R.J. Kavoussi, R.L. Hauger, T.B. Cooper, and C.F. Ferris, *Cerebrospinal* 

*Personality-Disordered Subjects.* Arch Gen Psychiatry, 1998. 55(8): p. 708-714. [184] Virkkunen, M., R. Rawlings, R. Tokola, R.E. Poland, A. Guidotti, C. Nemeroff, G.

[185] de Kloet, C.S., E. Vermetten, E. Geuze, V.M. Wiegant, and H.G.M. Westenberg,

[186] Pitman, R.K., S.P. Orr, and N.B. Lasko, *Effects of intranasal vasopressin and oxytocin on* 

[188] Gold, P., F. Goodwin, and V. Reus, *Vasopressin in affective illness.* The Lancet, 1978.

[189] Inder, W.J., R.A. Donald, T.C. Prickett, C.M. Frampton, P.F. Sullivan, R.T. Mulder, and

*posttraumatic stress disorder.* Psychiatry Research, 1993. 48(2): p. 107-117. [187] Yehuda, R., J. Flory, L. Pratchett, J. Buxbaum, M. Ising, and F. Holsboer, *Putative* 

*development of PTSD.* Psychopharmacology, 2010. 212(3): p. 405-417.

*and Healthy Volunteers.* Arch Gen Psychiatry, 1994. 51(1): p. 20-27.

Journal of Psychiatric Research, 2008. 42(3): p. 192-198.

*in depression.* Biol Psychiatry, 1997. 42: p. 744-747.

*fostering.* Social Neuroscience, 2010. 6(2): p. 156-168.

Endocrinology, 2008. 149(1): p. 116-121.

2004. 29(1): p. 35-48.

311(8076): p. 1233-1236.

Biological Psychiatry, 2010. 67(12): p. 1220-1222.

Psychoneuroendocrinology, 2011. 36(2): p. 294-297.

*differs n mice bred for high vs. low trait anxiety: Impact of brain vasopressin and cross-*

*anxiety-like behavior associated with discrete patterns of oxytocin and vasopressin 1a receptor density in the lateral septum.* Hormones and Behavior, 2012. 61(3): p. 454-461.

*Oxytocin and the Vasopressin (Avp) 1b Receptor Genes, But Not the Avp 1a Receptor Gene, Differentially Impairs the Bruce Effect in Laboratory Mice (Mus musculus).*

*Arginine Vasopressin Enhances the Encoding of Happy and Angry Faces in Humans.*

*Vasopressin selectively enhances recognition of sexual cues in male humans.*

*human acial responses related to social communication.* Psychoneuroendocrinology,

*Fluid Vasopressin Levels: Correlates With Aggression and Serotonin Function in* 

Bissette, K. Kalogeras, S.-L. Karonen, and M. Linnoila, *CSF Biochemistries, Glucose Metabolism, and Diurnal Activity Rhythms in Alcoholic, Violent Offenders, Fire Setters,* 

*Elevated plasma arginine vasopressin levels in veterans with posttraumatic stress disorder.*

*physiologic responding during personal combat imagery in Vietnam veterans with* 

*biological mechanisms for the association between early life adversity and the subsequent* 

P.R. Joyce, *Arginine vasopressin is associated with hypercortisolemia and suicide attempts* 


[176] Kessler, M.S., O.J. Bosch, M. Bunck, R. Landgraf, and I.D. Neumann, *Maternal care differs n mice bred for high vs. low trait anxiety: Impact of brain vasopressin and crossfostering.* Social Neuroscience, 2010. 6(2): p. 156-168.

78 Neuroendocrinology and Behavior

p. 391-395.

p. 403-411.

p. 63-72.

p. 1048-1054.

58(1): p. 107-116.

Neurosci, 1995. 15: p. 4250-4258.

Behavior, 2006. 49(4): p. 501-508.

Behav. Neurosci., 1999. 113: p. 1071-1079.

Journal of Neuroscience, 2010. 31(9): p. 1655-1663.

[161] Salomé, N., J. Stemmelin, C. Cohen, and G. Griebel, *Differential roles of amygdaloid nuclei* 

[162] Engelmann, M., M. Ludwig, and R. Landgraf, *Simultaneous monitoring of intracerebral* 

[163] Landgraf, R., R. Gerstberger, A. Montkowski, J.C. Probst, C.T. Wotjak, and F.

[164] Landgraf, R., E. Frank, J.M. Aldag, I.D. Neumann, X. Ren, and E.F. Terwilliger, *Viral* 

[165] Wersinger, S.R., H.K. Caldwell, L. Martinez, P. Gold, S.B. Hu, and W.S. Young,

[166] Aarde, S.M. and J.D. Jentsch, *Haploinsufficiency of the arginine–vasopressin gene is* 

[167] Alescio-Lautier, B., V. Paban, and B. Soumireu-Mourat, *Neuromodulation of memory in* 

[168] Gaffori, O.J.W. and D. De Wied, *Time-related memory effects of vasopressin analogues in rats.* Pharmacology Biochemistry and Behavior, 1986. 25(6): p. 1125-1129. [169] Young, L.J. and Z. Wang, *The neurobiology of pair bonding.* Nature Neurosci., 2004. 7(10):

[170] Cho, M.M., A.C. DeVries, J.R. Williams, and C.S. Carter, *The effects of oxytocin and* 

[171] Nephew, B.C. and R.S. Bridges, *Central actions of arginine vasopressin and a V1a receptor* 

[172] Nephew, B.C., E.M. Byrnes, and R.S. Bridges, *Vasopressin mediates enhanced offspring protection in multiparous rats.* Neuropharmacology, 2010. 58(1): p. 102-106. [173] Gutzler, S.J., M. Karom, W.D. Erwin, and H.E. Albers, *Arginine-vasopressin and the* 

[174] Caffrey, M.K., B.C. Nephew, and M. Febo, *Central vasopressin V1a receptors modulate* 

[175] Bosch, O.J. and I.D. Neumann, *Vasopressin released within the central amygdala promotes maternal aggression.* European Journal of Neuroscience, 2010. 31(5): p. 883-891.

Pharmacology Biochemistry and Behavior, 2008. 91(1): p. 77-83.

*in rats.* Psychopharmacology, 2006. 187(2): p. 237-244.

Genes, Brain and Behavior, 2007. 6(6): p. 540-551.

*n the anxiolytic- and antidepressant-like effects of the V1b receptor antagonist, SSR149415,* 

*release and behavior: vasopressin improves social recognition.* J Neuroendocrinol, 1994. 6:

Holsboer, *V1 vasopressin receptor antisense oligodeoxynucleotide into septum reduces vasopressin binding, social discrimination abilities, and anxiety-related behavior in rats.* J

*vector-mediated gene transfer of the vole V1a vasopressin receptor in the rat septum: improved social discrimination and active social behavior.* J Neuroendocrinol, 2003. 18:

*Vasopressin 1a receptor knockout mice have a subtle olfactory deficit but normal aggression.*

*associated with poor spatial working memory performance in rats.* Hormones and

*the hippocampus by vasopressin.* European Journal of Pharmacology, 2000. 405(1–3):

*vasopressin on partner preferences in male and female prairie voles (Microtus ochrogaster).*

*antagonist on maternal aggression, maternal behavior, and grooming in lactating rats.*

*regulation of aggression in female Syrian hamsters (Mesocricetus auratus).* European

*neural processing in mothers facing intruder threat to pups.* Neuropharmacology, 2010.


[190] Merali, Z., P. Kent, L. Du, P. Hrdina, M. Palkovits, G. Faludi, M.O. Poulter, T. Bédard, and H. Anisman, *Corticotropin-Releasing Hormone, Arginine Vasopressin, Gastrin-Releasing Peptide, and Neuromedin B Alterations in Stress-Relevant Brain Regions of Suicides and Control Subjects.* Biological Psychiatry, 2006. 59(7): p. 594-602.

Behavioral Roles of Oxytocin and Vasopressin 81

*variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans.* Proceedings of the National Academy of Sciences, 2008. 105(37):

*Arginine vasopressin 1a receptor gene and maternal behavior: evidence of association and* 

*humans is associated with changes in neuropeptides critical for regulating social behavior.* Proceedings of the National Academy of Sciences of the United States of America,

G. Daróczy, J.L. Kennedy, A. Vetró, M. Kovacs, C.L. Barr, and D. The International Consortium for Childhood-Onset Mood, *Further genetic evidence implicates the vasopressin system in childhood-onset mood disorders.* European Journal of

Kennedy, A. Vetro, M. Kovacs, C.L. Barr, and for the International Consortium for Childhood-Onset Mood Disorders, *Evidence of an Association Between the Vasopressin V1b Receptor Gene (AVPR1B) and Childhood-Onset Mood Disorders.* Arch Gen

*depression and depressive symptoms.* Journal of Affective Disorders, 2006. 91(2-3): p.

*Initial Severity and Antidepressant Benefits: A Meta-Analysis of Data Submitted to the* 

*oxytocin in the acute reinforcing effects and long-term adverse consequences of drug use?*

Bao, J. Shi, D.H. Epstein, Y. Shaham, and L. Lu, *A Memory Retrieval-Extinction Procedure to Prevent Drug Craving and Relapse.* Science, 2012. 336(6078): p. 241-245. [214] Zhou, Y., J.T. Bendor, V. Yuferov, S.D. Schlussman, A. Ho, and M.J. Kreek, *Amygdalar* 

*vasopressin mRNA increases in acute cocaine withdrawal: Evidence for opioid receptor* 

*Vasopressin and V1b Receptor in Heroin Withdrawal and Heroin Seeking Precipitated by* 

[204] Bisceglia, R., J.M. Jenkins, K.G. Wigg, T.G. O'Connor, G. Moran, and C.L. Barr,

[205] Fries, A.B.W., T.E. Ziegler, J.R. Kurian, S. Jacoris, and S.D. Pollak, *Early experience in* 

[206] Dempster, E.L., I. Burcescu, K. Wigg, E. Kiss, I. Baji, J. Gadoros, Z. Tamás, K. Kapornai,

[207] Dempster, E.L., I. Burcescu, K. Wigg, E. Kiss, I. Baji, J. Gadoros, Z. Tamas, J.L.

[208] Halbreich, U. and S. Karkun, *Cross-cultural and social diversity of prevalence of postpartum* 

[210] Kirsch, I., B.J. Deacon, T.B. Huedo-Medina, A. Scoboria, T.J. Moore, and B.T. Johnson,

[211] McGregor, I.S., P.D. Callaghan, and G.E. Hunt, *From ultrasocial to antisocial: a role for* 

[212] McGregor, I.S. and M.T. Bowen, *Breaking the loop: Oxytocin as a potential treatment for* 

[213] Xue, Y.-X., Y.-X. Luo, P. Wu, H.-S. Shi, L.-F. Xue, C. Chen, W.-L. Zhu, Z.-B. Ding, Y.-p.

[215] Zhou, Y., F. Leri, E. Cummins, M. Hoeschele, and M.J. Kreek, *Involvement of Arginine* 

*Stress and by Heroin.* Neuropsychopharmacology, 2007. 33(2): p. 226-236.

*Food and Drug Administration.* PLoS Med, 2008. 5(2): p. e45.

British Journal of Pharmacology, 2008. 154(2): p. 358-368.

*modulation.* Neuroscience, 2005. 134(4): p. 1391-1397.

*drug addiction.* Hormones and Behavior, 2012. 61(3): p. 331-339.

*moderation.* Genes, Brain and Behavior, 2012. 11(3): p. 262-268.

p. 14153-14156.

97-111.

2005. 102(47): p. 17237-17240.

Neuroscience, 2009. 30(8): p. 1615-1619.

Psychiatry, 2007. 64(10): p. 1189-1195.

[209] Hammen, C., *Stress and depression*. 2005. p. 293-319.


*variation in the vasopressin receptor 1a gene (AVPR1A) associates with pair-bonding behavior in humans.* Proceedings of the National Academy of Sciences, 2008. 105(37): p. 14153-14156.


80 Neuroendocrinology and Behavior

292.

[190] Merali, Z., P. Kent, L. Du, P. Hrdina, M. Palkovits, G. Faludi, M.O. Poulter, T. Bédard,

*Suicides and Control Subjects.* Biological Psychiatry, 2006. 59(7): p. 594-602. [191] Goekoop, J.G., R. de Winter, R. Wolterbeek, and V. Wiegant, *Support for two increased* 

[193] van West, D., J. Del-Favero, Y. Aulchenko, P. Oswald, D. Souery, T. Forsgren, S. Sluijs,

[194] Manning, M., A. Misicka, A. Olma, K. Bankowski, S. Stoev, B. Chini, T. Durroux, B.

[195] Manning, M., S. Stoev, B. Chini, T. Durroux, B. Mouillac, G. Guillon, D.N. Inga, and L.

[196] Beckwith, B.E., T.V. Petros, P.J. Bergloff, and R.J. Staebler, *Vasopressin analogue (ddavp) acilitates recall of narrative prose.* Behavioral Neuroscience, 1987. 101(3): p. 429-432. [197] Pietrowsky, R., G. Fehm-Wolfsdorf, J. Born, and H.L. Fehm, *Effects of DGAVP on verbal* 

[198] Beckwith, B.E., D.I. Couk, and T.S. Till, *Vasopressin analog influences the performance of* 

[199] Perras, B., C. Droste, J. Born, H.L. Fehm, and R. Pietrowsky, *Verbal memory after three* 

[200] Koob, G.F., C. Lebrun, R.-M. Bluthé, R. Dantzer, and M. Le Moal, *Role of neuropeptides* 

[201] Le Moal, M., R. Dantzer, B. Michaud, and G.F. Koob, *Centrally injected arginine* 

[202] Jing, W., F. Guo, L. Cheng, J.-F. Zhang, and J.-S. Qi, *Arginine vasopressin prevents* 

[203] Walum, H., L. Westberg, S. Henningsson, J.M. Neiderhiser, D. Reiss, W. Igl, J.M.

*months of intranasal vasopressin in healthy old humans.* Psychoneuroendocrinology,

*in earning versus performance: Focus on vasopressin.* Brain Research Bulletin, 1989.

*vasopressin (AVP) facilitates social memory in rats.* Neurosci. Lett., 1987. 77: p. 353-359.

*amyloid β protein-induced impairment of long-term potentiation in rat hippocampus in* 

Ganiban, E.L. Spotts, N.L. Pedersen, E. Eriksson, and P. Lichtenstein, *Genetic* 

*males on a reaction time task.* Peptides, 1983. 4(5): p. 707-709.

*vivo.* Neuroscience Letters, 2009. 450(3): p. 306-310.

*treatment.* Journal of Psychopharmacology, 2010. 25(10): p. 1304-1312. [192] Goekoop, J.G., R.P.F. de Winter, R. de Rijk, K.H. Zwinderman, A. Frankhuijzen-

*retardation.* Psychiatry Research, 2006. 141(2): p. 201-211.

Neuroendocrinology, 2012. 24(4): p. 609-628.

*in Brain Research*. 2008, Elsevier. p. 473-512.

*memory.* Peptides, 1988. 9(6): p. 1361-1366.

1997. 22(6): p. 387-396.

23(4–5): p. 359-364.

and H. Anisman, *Corticotropin-Releasing Hormone, Arginine Vasopressin, Gastrin-Releasing Peptide, and Neuromedin B Alterations in Stress-Relevant Brain Regions of* 

*vasopressinergic activities in depression at large and the differential effect of antidepressant* 

Sierevogel, and V.M. Wiegant, *Depression with above-normal plasma vasopressin: Validation by relations with family history of depression and mixed anxiety and* 

S. Bel-Kacem, R. Adolfsson, J. Mendlewicz, C. Van Duijn, D. Deboutte, C. Van Broeckhoven, and S. Claes, *A major SNP haplotype of the arginine vasopressin 1B receptor protects against recurrent major depression.* Mol Psychiatry, 2004. 9(3): p. 287-

Mouillac, M. Corbani, and G. Guillon, *Oxytocin and Vasopressin Agonists and Antagonists as Research Tools and Potential Therapeutics.* Journal of

Rainer, *Peptide and non-peptide agonists and antagonists for the vasopressin and oxytocin V1a, V1b, V2 and OT receptors: research tools and potential therapeutic agents*, in *Progress* 


[216] Edwards, S., M. Guerrero, O.M. Ghoneim, E. Roberts, and G.F. Koob, *Evidence that vasopressin V1b receptors mediate the transition to excessive drinking in ethanol-dependent rats.* Addiction Biology, 2012. 17(1): p. 76-85.

**Chapter 4** 

© 2012 Sumiyoshi et al., licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2012 Sumiyoshi et al., licensee InTech. This is a paper distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

**Role for Pituitary Neuropeptides in Social** 

Derangement of hormonal milieu has been associated with the pathophysiology of psychiatric illnesses, such as schizophrenia, mood disorders, and developmental disorders [1; 2; 3]. Among them, schizophrenia is a relatively common neuropsychiatric disorder, and has been associated with debilitating consequences if not treated properly [4; 5]. The illness is characterized by positive (e.g., delusions, hallucinations, bizarre thoughts) and negative (blunt affect, avolition, anhedonia, social withdrawal) symptoms, as well as deficits in various cognitive abilities, e.g. verbal memory, working memory, attention/vigilance, and information processing [4; 6; 7]. Minor impairments of social cognition are often observed

The role for endocrinological dysregulation in the development of psychotic symptoms has been suggested by brain imaging studies. For example, a larger than normal volume of the pituitary gland has been reported in patients with first-episode schizophrenia [9] (Fig. 1). Further, these patients exhibit an increase in the pituitary volume overtime, unlike the case with normal volunteers, the degree of which is correlated with the change in positive symptoms [9]. These findings, representing mainly a morphological change of the anterior pituitary [9], are consistent with the concept of HPA axis hyperactivity in response to stress

Hormones secreted from the posterior portion of the pituitary gland, i.e. vasopressin and oxytocin, have also been a focus in schizophrenia research from the perspective of social behavior disturbances [2; 11; 12]. In this chapter, we provide an overview of preclinical and clinical evidence for contribution of the vasopressin and oxytocin systems in social behavior deficits of schizophrenia and related disorders, as well as their treatment. Related discussions on the role of these neuropeptides in the coping of stressors and psychiatric

**Behavior Disturbances of Schizophrenia** 

Tomiki Sumiyoshi, Tadasu Matsuoka and Masayoshi Kurachi

Additional information is available at the end of the chapter

during the premorbid stage of the disease [8].

conditions are provided in other Chapters [3; 13].

during psychotic experience [10].

http://dx.doi.org/10.5772/52326

**1. Introduction** 

