CCK as a central satiety factor: behavioral and electrophysiological evidence

Abstract

CCK and its derivatives potently inhibit feeding, even after vagotomy. This effect is thus considered to be peripheral. Recently, however, the vagal gastric branch was reported to essentially bring feeding inhibition into full play. In the present study, it was found that CCK-8, administered into the third cerebroventricle (III-cv), or into the lateral hypothalamus (LHA), significantly and dose-dependently inhibited feeding induced by electrical stimulation of the contralateral LHA (LHA-ESIF) in the chronic rat. This inhibition by CCK-8 was not affected by systemic pretreatment with proglumide (1 mg), a selective antagonist, while CCK (250 ng) simultaneously microinjected into the III-cv with 5 micrograms proglumide almost completely eliminated the CCK effect on LHA-ESIF. Neuronal activity of the ventromedial hypothalamus (VMH) was enhanced, and that of the LHA was suppressed by electrophoretic direct application of CCK on neurons in urethane-chloralose-anesthetized rats. CCK also markedly decreased the threshold of VMH glucose responding neurons. These results indicate that the satiety effect is not only peripheral, but might also be central, especially through feeding-related hypothalamic neurons, which are probably important in feeding inhibition.