Effects of paraventricular nucleus injection of CCK-8 on plasma CCK-8 levels in rats

The aim of the study was to determine whether paraventricular nucleus (PVN) injection of an anorexic 500-pmol dose of cholecystokinin (CCK)-8 could increase plasma CCK-8 levels sufficiently to suppress feeding by a peripheral mechanism. Rats received PVN injections of CCK-8 either alone or with H-3-labelled propionylated CCK-8 (H-3-pCCK-8) and plasma samples were taken at various times from 3 to 120 min post-injection. Plasma CCK-8 levels were estimated from measurements of both total plasma CCK-like immunoreactivity (CCK-LI) and H-3-pCCK-8 activity. PVN injections of CCK-8 and 3H-pCCK-8 produced estimated peak increases in plasma CCK-8 of 15 +/- 11 and 22 +/- 3 pM, respectively. The i.v. infusion of CCK-8 doses (0.2 and 1 nmol/kg h) that bracketed the threshold dose for suppression of feeding, increased plasma CCK-LI from a basal level of 6 +/- 1 to 49 +/- 10 and 166 +/- 36 pM, respectively. The i.v. injections of 600 and 4800 pmol of CCK-8 did not suppress feeding. These results suggest that PVN injection of an anorexic 500-pmol dose of CCK-8 does not increase plasma CCK-8 levels sufficiently to suppress feeding by a peripheral mechanism. (C) 2000 Elsevier Science B.V. All rights reserved.