CHOLECYSTOKININ-OCTAPEPTIDE (CCK-8) INJECTED INTO A CEREBRAL VENTRICLE INDUCES A FEVER-LIKE THERMOREGULATORY RESPONSE MEDIATED BY TYPE-B CCK-RECEPTORS IN THE RAT

In conscious female Wistar rats with chronic lateral cerebroventricular cannula, the thermoregulatory effects of CCK-8, ceruletide and prostaglandin E(1)(PGE(1)) were studied. In addition, the possible involvement of type A or type B receptors of CCK-8 in thermoregulatory effects of PGE(1) and CCK-8 was also investigated. In the normothermic rat an intracerebroventricular (i.c.v.) injection of CCK-8 or ceruletide induced a thermogenic response with tail-skin vasoconstriction and a resulting rise in colonic temperature (T-c). There was a significant negative correlation between the starting level of T-c and the extent of rise in T-c following an i.c.v. administration of PGE(1), CCK-8 or ceruletide. Subcutaneously injected CCK-8 caused decreases in T-c in a cool ambient temperature as also described by others. The fever-like response to i.c.v. injected CCK-8 was attenuated by a CCK type B receptor blocker, but not by a CCK type A receptor blocker. Conversely, the hypothermic response to peripherally administered CCK-8 was attenuated by a type A receptor blocker, but not by a type B receptor blocker. Neither of these CCK-receptor blockers influenced the fever caused by an i.c.v. injection of PGE(1). It is concluded that in normothermic rats the thermogenic response observed after i.c.v. injection of CCK-8 and ceruletide is the most likely central thermoregulatory change mediated by CCK type B receptors, while the well-known hypothermic response observed after peripheral injection of these peptides might also be explained by their direct effect on variables influencing some of the thermoregulatory effector mechanisms at the periphery.