Cholecystokinin octapeptide (CCK-8) injected into a cerebral ventricle induces a fever-like thermoregulatory response mediated by type B CCK-receptors in the rat

Abstract

In conscious female Wistar rats with chronic lateral cerebroventricular cannula, the thermoregulatory effects of CCK-8, ceruletide and prostaglandin E1 (PGE1) were studied. In addition, the possible involvement of type A or type B receptors of CCK-8 in thermoregulatory effects of PGE1 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 (Tc). There was a significant negative correlation between the starting level of Tc and the extent of rise in Tc following an i.c.v. administration of PGE1, CCK-8 or ceruletide. Subcutaneously injected CCK-8 caused decreases in Tc 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 PGE1. 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.