**6. References**


<sup>\*</sup> Corresponding Author

[8] L. Erlenmeyer-Kimling, D. Rock, S.A. Roberts, M. Janal, C. Kestenbaum, B. Cornblatt, U.H. Adamo, Gottesman, II, Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project. Am J Psychiatry 157 (2000) 1416-1422.

Role for Pituitary Neuropeptides in Social Behavior Disturbances of Schizophrenia 93

[22] R. Dantzer, R.M. Bluthe, G.F. Koob, M. Le Moal, Modulation of social memory in male

[23] M. Le Moal, R. Dantzer, B. Michaud, G.F. Koob, Centrally injected arginine vasopressin

[24] G.J. De Vries, R.M. Buijs, The origin of the vasopressinergic and oxytocinergic innervation of the rat brain with special reference to the lateral septum. Brain Res 273

[25] J.N. Ferguson, J.M. Aldag, T.R. Insel, L.J. Young, Oxytocin in the medial amygdala is

[26] M. Joels, Modulatory actions of steroid hormones and neuropeptides on electrical

[27] T. Matsuoka, M. Tsunoda, T. Sumiyoshi, I. Takasaki, Y. Tabuchi, T. Seo, K. Tanaka, T. Uehara, H. Itoh, M. Suzuki, M. Kurachi, Effect of MK-801 on gene expressions in the

[28] P.R. Lee, D.L. Brady, R.A. Shapiro, D.M. Dorsa, J.I. Koenig, Social interaction deficits caused by chronic phencyclidine administration are reversed by oxytocin.

[29] P.R. Lee, D.L. Brady, R.A. Shapiro, D.M. Dorsa, J.I. Koenig, Prenatal stress generates deficits in rat social behavior: Reversal by oxytocin. Brain Res 1156 (2007) 152-167. [30] D. Jin, H.X. Liu, H. Hirai, T. Torashima, T. Nagai, O. Lopatina, N.A. Shnayder, K. 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, H. Higashida, CD38 is critical for social behaviour by

[31] C. Sumiyoshi, T. Sumiyoshi, A. Roy, K. Jayathilake, H.Y. Meltzer, Atypical antipsychotic drugs and organization of long-term semantic memory: multidimensional scaling and cluster analyses of category fluency performance in schizophrenia. Int J

[32] C. Sumiyoshi, A. Ertugrul, A.E. Anil Yagcioglu, Semantic memory deficits based on category fluency performance in schizophrenia: Similar impairment patterns of semantic organization across Turkish and Japanese patients. Psychiatry Res

[33] S.R. McGurk, The effect of clozapine on cognitive functioning in schizophrenia. J Clin

[34] N.D. Woodward, S.E. Purdon, H.Y. Meltzer, D.H. Zald, A meta-analysis of neuropsychological change to clozapine, olanzapine, quetiapine, and risperidone in

[35] T. Sumiyoshi, K. Jayathilake, H.Y. Meltzer, The effect of melperone, an atypical antipsychotic drug, on cognitive function in schizophrenia. Schizophr Res 59 (2003) 7-16. [36] M. Bubenikova-Valesova, M. Votava, J. Palenicek, J. Horacek, C. Hoschl, Effect of serotonin-1A receptors on behavioral changes in animal model of schizophrenia-like

rats by neurohypophyseal peptides. Psychopharmacology 91 (1987) 363-368.

(AVP) facilitates social memory in rats. Neurosc Lett 77 (1987) 353-359.

essential for social recognition in the mouse. Neurosc 21 (2001) 8278-8285.

activity in brain. Eur J Pharmacol 405 (2000) 207-216.

Neuropsychopharmacology 30 (2005) 1883-1894.

regulating oxytocin secretion. Nature 446 (2007) 41-45.

schizophrenia. Int J Neuropsychopharmacol 8 (2005) 457-472.

behavior, in, 16th European Congress of Psychiatry, Nice, France, 2008.

Neuropsychopharmacol 9 (2006) 677-683.

Psychiatry 60 (suppl 12) (1999) 24-29.

(2009)167:47-57..

amygdala of rats. Synapse 62 (2008) 1-7.

(1983) 307-317.


[22] R. Dantzer, R.M. Bluthe, G.F. Koob, M. Le Moal, Modulation of social memory in male rats by neurohypophyseal peptides. Psychopharmacology 91 (1987) 363-368.

92 Neuroendocrinology and Behavior

Psychiatry 157 (2000) 1416-1422.

Schizoph Res 98 (2008) 247-255.

Neuron 47 (2005) 503-513.

Brain Res 1053 (2005) 131-136.

behavior. Neuron 47 (2005) 483-486.

Natl Acad Sci U S A 102 (2005) 17237-17240.

interaction in the rat. Brain Res 992 (2003) 239-245.

[8] L. Erlenmeyer-Kimling, D. Rock, S.A. Roberts, M. Janal, C. Kestenbaum, B. Cornblatt, U.H. Adamo, Gottesman, II, Attention, memory, and motor skills as childhood predictors of schizophrenia-related psychoses: the New York High-Risk Project. Am J

[9] T. Takahashi, S.Y. Zhou, K. Nakamura, R. Tanino, A. Furuichi, M. Kido, Y. Kawasaki, K. Noguchi, H. Seto, M. Kurachi, M. Suzuki, Longitudinal volume changes of the pituitary gland in patients with schizotypal disorder and first-episode schizophrenia. Prog in

[10] C.M. Pariante, K. Vassilopoulou, D. Velakoulis, L. Phillips, B. Soulsby, S.J. Wood, W. Brewer, D.J. Smith, P. Dazzan, A.R. Yung, I.M. Zervas, G.N. Christodoulou, R. Murray, P.D. McGorry, C. Pantelis, Pituitary volume in psychosis. J Psychiatry : 185 (2004) 5-10. [11] T. Sumiyoshi, T. Matsuoka, K. Tanaka, V. Bubenikova-Valesova, Social interaction deficits in schizophrenia-spectrum disorders and pharmacologic intervention, in: A.T. Heatherton, V.A. Walcott, (Eds.), Handbook of Social Interactions in the 21st Century,

[12] O. Teltsh, K. Kanyas-Sarner, A. Rigbi, L. Greenbaum, B. Lerer, Y. Kohn, Oxytocin and vasopressin genes are significantly associated with schizophrenia in a large Arab-Israeli

[13] B.C. Nephew, Behavioral roles of oxytocin and vasopressin, in: T. Sumiyoshi, (Ed.),

[14] M. Goldman, M. Marlow-O'Connor, I. Torres, C.S. Carter, Diminished plasma oxytocin in schizophrenic patients with neuroendocrine dysfunction and emotional deficits.

[15] A.B. Fries, T.E. Ziegler, J.R. Kurian, S. Jacoris, S.D. Pollak, Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior. Proc

[16] I.F. Bielsky, S.B. Hu, X. Ren, E.F. Terwilliger, L.J. Young, The V1a vasopressin receptor is necessary and sufficient for normal social recognition: a gene replacement study.

[17] T. Matsuoka, T. Sumiyoshi, K. Tanaka, M. Tsunoda, T. Uehara, H. Itoh, M. Kurachi, NC-1900, an arginine-vasopressin analogue, ameliorates social behavior deficits and hyperlocomotion in MK-801-treated rats: therapeutic implications for schizophrenia.

[18] K. Tanaka, M. Suzuki, T. Sumiyoshi, M. Murata, M. Tsunoda, M. Kurachi, Subchronic phencyclidine administration alters central vasopressin receptor binding and social

[19] E.E. Storm, L.H. Tecott, Social circuits: peptidergic regulation of mammalian social

[20] D. de Wied, J.M. van Ree, Neuropeptides: animal behaviour and human

[21] J.T. Winslow, N. Hastings, C.S. Carter, C.R. Harbaugh, T.R. Insel, A role for central vasopressin in pair bonding in monogamous prairie voles. Nature 365 (1993) 545-548.

psychopathology. Eur Arch Psychiatr Neurol Sci 238 (1989) 323-331.

Neuro-Psychopharmacology & Biol Psychiat 35 (2011) 177-183.

Nova Science Publishers, New York, 2009, pp. 363-370.

Neuroendocrinology and Behavior, InTech, Rijeka, 2012, pp. ( ).

pedigree. Int. Neuropsychopharmacol (2011) 1-11.


[37] J. Horacek, V. Bubenikova-Valesova, M. Kopecek, T. Palenicek, C. Dockery, P. Mohr, C. Hoschl, Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs 20 (2006) 389-409.

**Chapter 5** 

© 2012 Munesue 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 Munesue 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.

**Is Intranasal Administration of Oxytocin** 

Toshio Munesue, Kazumi Ashimura, Hideo Nakatani, Mitsuru Kikuchi, Shigeru Yokoyama, Manabu Oi, Haruhiro Higashida and Yoshio Minabe

The neuropeptide oxytocin (OT) is synthesized in magnocellular neurons of the paraventricular and supraoptic nuclei of the hypothalamus and released from axon terminals in the neurohypophysis into the general circulation. However, OT is also released from somata and dendrites of magnocellular neurons into the brain [1]. OT release from axon terminals, somata and dendrites is regulated by not only activity-dependent Ca2+ influx, but also by mobilization of Ca2+ from intracellular Ca2+ stores [2, 3]. CD38, a transmembrane glycoprotein with ADP-ribosyl cyclase activity, plays a critical role in mobilization of intracellular Ca2+, and therefore CD38 gene knockout (CD38-/-) mice show low plasma OT concentrations [2]. On the other hand, CD38 is not responsible for the

secretion of arginine vasopressin, which is another neurohypophyseal hormone [2].

Perioherally, OT promotes milk ejection in females and penile erection in males [4]. In addition, studies using OT gene knockout (OT-/-), OT receptor gene knockout (OTR-/-), or CD38-/- mice, in which OT signaling would be disrupted, were performed to investigate the

While OT+/+ male mice showed a decline in the time investigating a female mouse during repeated pairings with full recovery following the introduction of a new female, OT-/- male mice show no such decline [7]. The results suggested that OT-/- male mice fail to develop social memory. Moreover, in a different experimental paradigm, OT-/- mice showed the same sociability, which was reflected as more time spent with a novel mouse as compared to time spent with a novel object, and preference for social novelty, which is reflected as more time spent with a second novel mouse as compared to time spent with a non-stranger mouse, as

**Effective for Social Impairments in** 

**Autism Spectrum Disorder?** 

Additional information is available at the end of the chapter

roles of OT in the central nervous system [5, 6].

http://dx.doi.org/10.5772/48798

**1. Introduction** 


**Chapter 5** 
