Effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons in rats lacking CCK-A receptor

Hirofumi Hashimoto, Tatsushi Onaka, Makoto Kawasaki, Lei Chen, Takashi Mera, Atsushi Soya, Takeshi Saito, Hiroaki Fujihara, Hiroyoshi Sei, Yusuke Morita, Yoichi Ueta

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Peripheral administration of cholecystokinin (CCK)-8 selectively activates oxytocin (OXT)-secreting neurons in the supraoptic (SON) and the paraventricular nuclei (PVN) with the elevation of plasma OXT level in rats. We examined the effects of intravenous (iv) administration of CCK-8 on the neuronal activity of hypothalamic OXT-secreting neurons and plasma OXT level in Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a congenital defect in the expression of the CCK-A receptor gene. In situ hybridization histochemistry (ISH) for c-fos mRNA revealed that the expression of the c-fos gene was not induced in the SON, the PVN, the nucleus of the tractus solitarius (NTS) and the area postrema (AP) 30 min after iv administration of CCK-8 (20 and 40 μg/kg) in OLETF rats. In Long-Evans Tokushima Otsuka (LETO) rats (controls), c-fos mRNA was detected abundantly in those nuclei 30 min after iv administration of CCK-8 (20 μg/kg). Immunohistochemistry for c-fos protein (Fos) showed that the distributions of Fos-like immunoreactivity (LI) were identical to the results obtained from ISH. Dual immunostaining for OXT and Fos revealed that Fos-LI was mainly observed in OXT-secreting neurons in the SON and the PVN of LETO rats 90 min after iv administration of CCK-8 (20 μg/kg). Radioimmunoassay for OXT and arginine vasopressin (AVP) showed that iv administration of CCK-8 did not cause significant change in the plasma OXT and AVP levels in OLETF rats, while iv administration of CCK-8 caused a significant elevation of plasma OXT level without changing the plasma AVP level in LETO rats. These results suggest that peripheral administration of CCK-8 may selectively activate the hypothalamic OXT-secreting neurons and brainstem neurons through CCK-A receptor in rats.

Original languageEnglish
Pages (from-to)16-25
Number of pages10
JournalAutonomic Neuroscience: Basic and Clinical
Issue number1-2
StatePublished - Aug 31 2005

Bibliographical note

Funding Information:
This study was supported by Grant-in-Aid for Scientific Research (B) No. 16390061 from the Ministry of Education, Culture, Sports, Science and Technology and a grant from Ajinomoto Co. Ltd (Japan).


  • CCK-A receptor
  • Otsuka Long-Evans Tokushima Fatty rat
  • Oxytocin
  • Paraventricular nucleus
  • Supraoptic nucleus

ASJC Scopus subject areas

  • Endocrine and Autonomic Systems
  • Clinical Neurology
  • Cellular and Molecular Neuroscience


Dive into the research topics of 'Effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons in rats lacking CCK-A receptor'. Together they form a unique fingerprint.

Cite this