Effects of ceruletide and haloperidol on the hypothalamo-pituitary beta-endorphin system and brain beta-endorphin contents in the rat: with special reference to effects of ceruletide in chronically haloperidol-treated rats.
Subcutaneous (sc) administration of 200 micrograms/kg ceruletide (CER), a decapeptide chemically related CCK-8, and 5 mg/kg haloperidol (HLP) to rats increased the plasma immunoreactive beta-endorphin (ir-beta-END) level. The combined injection of CER and haloperidol caused higher plasma ir-beta-END levels than either drug alone. High plasma ir-beta-END levels returned to control levels on the 2nd day. Prior intraperitoneal (ip) administration of a CCK receptor antagonist, L-364,718 (3 mg/kg), but not proglumide (400 mg/kg, ip), inhibited CER-induced, but not HLP-induced, elevation in plasma ir-beta-END levels. The dopamine agonist, bromocriptine (1 mg/kg, ip) decreased plasma ir-beta-END levels, but had not effect on CER-induced elevation in plasma ir-beta-END levels, whereas bromocriptine-induced reduction in plasma ir-beta-END levels was antagonised by HLP. CER injection to chronically HLP-treated rats caused a greater elevation of plasma ir-beta-END levels compared to saline-injected rats. In contrast to the acute experiment, plasma ir-beta-END levels remained elevated over a period of 24 h. In the acute experiment, CER, HLP or the combined treatment with these two drugs had no effect on ir-beta-END contents in the pituitary gland and brain. In the chronic experiment, HLP increased the adenohypophyseal and septal ir-beta-END contents and decreased the hippocampal ir-beta-END contents 24 h after the final HLP injection. CER caused a small reduction only in the hippocampal ir-beta-END contents of CER-injected rats 15 min after injection. When determined on the 2nd day, however, the increases in the adenohypophyseal and septal ir-beta-END contents and the decrease in the hippocampal ir-beta-END contents observed in CER-injected rats were of the same magnitude as those of rats not given the CER injection. These findings indicate that CER stimulates the release of ir-beta-END from the adenohypophysis through CCK-A receptors and that elevated plasma ir-beta-END levels is partly involved in some behavioural effects induced by CER. Furthermore, sustained elevation of plasma ir-beta-END levels after a single injection of CER to chronically HLP-treated rats may explain its long-lasting therapeutic and behavioural effects.
Hagino
Y
Y
Department of Psychopharmacology, Psychiatric Research Institute of Tokyo, Japan.
Okuwa
M
M
Moroji
T
T
D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D001971:Bromocriptine / Q000494:pharmacology; D002108:Ceruletide / Q000008:administration & dosage / Q000494:pharmacology*; D020109:Devazepide; D004347:Drug Interactions; D006220:Haloperidol / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011377:Proglumide / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000378:metabolism; D001615:beta-Endorphin / Q000097:blood / Q000378:metabolism*; D008083:beta-Lipotropin / Q000378:metabolism
D001570:Benzodiazepinones; D011949:Receptors, Cholecystokinin; D001971:Bromocriptine; D001615:beta-Endorphin; D002108:Ceruletide; D008083:beta-Lipotropin; D011377:Proglumide; D006220:Haloperidol; D020109:Devazepide