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 in crease 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 es timated from measurements of both total plasma CCK-like immunoreactivity (C CK-LI) and H-3-pCCK-8 activity. PVN injections of CCK-8 and 3H-pCCK-8 produ ced 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 b racketed the threshold dose for suppression of feeding, increased plasma CC K-LI from a basal level of 6 +/- 1 to 49 +/- 10 and 166 +/- 36 pM, respecti vely. The i.v. injections of 600 and 4800 pmol of CCK-8 did not suppress fe eding. These results suggest that PVN injection of an anorexic 500-pmol dos e of CCK-8 does not increase plasma CCK-8 levels sufficiently to suppress f eeding by a peripheral mechanism. (C) 2000 Elsevier Science B.V. All rights reserved.