RESUMEN
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.