PERIPHERAL ADMINISTRATION OF CHOLECYSTOKININ ACTIVATES C-FOS EXPRESSION IN THE LOCUS COERULEUS SUBCOERULEUS NUCLEUS, DORSAL VAGAL COMPLEX AND PARAVENTRICULAR NUCLEUS VIA CAPSAICIN-SENSITIVE VAGAL AFFERENTS ANDCCK-A RECEPTORS IN THE RAT/

Intraperitoneal (i.p.) administration of sulfated CCK octapeptide (CCK -8S) has been shown to induce changes in neuronal activity in the nucl eus of the solitary tract (NTS) and area postrema (AP), sensory parts of the dorsal vagal complex (DVC), and in the paraventricular nucleus of the hypothalamus (PVN), as determined by activation of c-fos expres sion. Whether peripheral CCK influences neuronal activity in the locus coeruleus (LC)/subcoeruleus nucleus (SC) was investigated in awake ra ts at intraperitoneal (i.p.) injection of CCK-8S by c-Fos immunohistoc hemistry. CCK-8S i.p. (25, 50, and 100 mu g/kg, respectively) dose-dep endently increased the average number of c-Fos-LI-positive cells/secti on in the LC/SC by the factor 5.9, 8.2, and 11.7, respectively. Pretre atment with the CCK-A receptor antagonist MK-329 (devazepide; 1 mg/kg and 2 mg/kg i.p.) reduced the CCK-induced increase in c-fos expression in the LC/SC by 54% and 75%, respectively; the CCK-B receptor antagon ist L-365,260 had no effect. Perivagal capsaicin pretreatment diminish ed the CCK-induced increase in the number of c-Fos-LI-positive cells i n the LC/SC by 65%. In comparison, the CCK-A antagonist devazepide (1 mg/kg and 2 mg/kg i.p.) reduced the increase in c-fos expression by 76 % and 88% in the PVN, 69% and 88% in the NTS, 86% and 83%, respectivel y, in the AP. Capsaicin diminished the CCK-induced increase in c-Fos-L I-positive cells in the PVN by 64%, in the NTS by 60%, but in the AP o nly by 25%. Immunostaining against the nuclear antigen c-Fos and the c ytoplasmatic antigen tyrosine hydroxylase (TH) showed that 40% of all c-Fos-LI-positive cells in the LC/SC were TH-LI positive at 25 mu g CC K/kg. The data indicate that CCK-8S i.p. induces modulation of neurona l activity in the LC/SC, DVC and PVN predominantly by peripheral actio n on CCK-A receptors and capsaicin-sensitive vagal afferents. These fi ndings suggest that the LC/SC is involved in CNS-mediated regulatory i nfluences of peripheral CCK. (C) 1997 Elsevier Science B.V.