Excitatory effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons via CCK-A receptor

Abstract

Peripheral administration of cholecystokinin (CCK)-8 causes an activation of oxytocin (OXT) -secreting neurons in the paraventricular (PVN) and supraoptic nuclei (SON) with elevation of plasma OXT level in rats. In the present study, we investigated the effects of intravenous (iv) administration of CCK-8 on OXT-secreting neurons in the PVN and SON of Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a congenital defect in the expression of the CCK-A receptor gene, using in situ hybridization histochemistry (ISH) for c-fos mRNA and immunohistochemistry for Fos. Although c-fos mRNA was detected in the PVN and the dorsal parts of the SON of LETO (control) rats 30 minutes after iv administration of CCK-8, c-fos mRNA was not detected in the PVN and SON of OLETF rats. The distributions of Fos-like immunoreactivity (LI) were identical to the results obtained from ISH. After iv administration of saline, c-fos mRNA and Fos-LI were not detected in the hypothalamus of both OLETF and LETO rats. Dual staining for OXT and Fos revealed that Fos-LI was mainly observed in OXT-secreting neurons in the PVN and SON of LETO rats after iv administration of CCK-8. These results suggest that CCK-8 may activate OXT-secreting neurons in the rat PVN and SON through CCK-A receptor. [Jpn J Physiol 54 Suppl:S217 (2004)]