EVIDENCE THAT CHOLECYSTOKININ INDUCES IMMEDIATE-EARLY GENE-EXPRESSIONIN THE BRAIN-STEM, HYPOTHALAMUS AND AMYGDALA OF THE RAT BY A CCKA RECEPTOR MECHANISM

The effect of sulphated cholecystokinin octapeptide (CCK-8S) on immedi ate early gene expression in the rat CNS was investigated using the te chnique of in situ hybridization. A rapid and transient induction of c -fos, NGFI-A and NGFI-B (nerve growth factor-induced genes A and B) mR NA was demonstrated in the nucleus tractus solitarius (NTS), area post rema (AP), hypothalamic paraventricular (PVN) and supraoptic (SON) nuc lei, and central nucleus of the amygdala, following peripheral adminis tration of CCK-8S (1-100 mu g/kg i.p.). In contrast, levels of c-jun, jun B and jun D mRNA were unaffected by the peptide. The closely relat ed decapeptide, caerulein (50 mu g/kg i.p.), induced the same pattern of IEG expression as CCK-8S, whereas the desulphated octapeptide, CCK- 8DS (50 mu g/kg i.p.), had no effect on levels of mRNA for any IEG stu died. Expression of IEG mRNA in these areas was suppressed by bilatera l subdiaphragmatic vagotomy, and by pretreatment with the selective CC KA receptor antagonist, devazepide (0.1 and 1 mg/kg i.p.). In contrast , CCK-8S induction of IEG mRNA was not blocked by pretreatment with th e selective CCKB receptor antagonist, CI-988 (1 or 10 mg/kg i.p.). In addition, the selective CCKB receptor agonists, CCK-4 (50 mu g/kg i.p. ) or pentagastrin (2 mg/kg i.p.), failed to induce IEG expression in a ny of the areas studied. These results suggest that systemic CCK-8S pr imarily acts via CCKA receptors on vagal afferents to stimulate IEG mR NA expression in the rat CNS.