Brain regions where cholecystokinin suppresses feeding in rats

The gut-brain peptide, cholecystokinin (CCK), inhibits food intake when inj ected either systemically or within the brain. To determine whether CCK's e ffect in the brain is anatomically specific, CCK-8 (0.8, 4, 20, 100, 500 pm ol) was microinjected into one of 14 different brain sites of rats, and its impact on subsequent food intake was measured. CCK-8 at 500 pmol significa ntly suppressed intake during the first hour post-injection following admin istration into six hypothalamic sites (anterior hypothalamus, dorsomedial h ypothalamus, lateral hypothalamus, paraventricular nucleus, supraoptic nucl eus, ventromedial hypothalamus) and two hindbrain sites (nucleus tractus so litarius, fourth ventricle). Although lower doses were sometimes effective (anterior hypothalamus, dorsomedial hypothalamus, nucleus tractus solitariu s), there appeared to be no significant difference in potency among sites. Injections into the medial amygdala, nucleus accumbens, posterior hypothala mus, dorsal raphe, and ventral tegmental area were either ineffective or pr oduced a delayed response. The higher doses required for most sites, as wel l as the widespread effectiveness of CCK-8 within the hypothalamus, suggest that spread of CCK-8 to adjacent brain sites, and (or) to the periphery, m ay have been required for anorexia to occur. Findings reported in an accomp anying paper provide strong evidence that paraventricular nucleus injection of CCK-8 (500 pmol) did not increase plasma CCK-levels sufficiently to sup press feeding by a peripheral mechanism. Together, these results suggest th at CCK may be acting as a neurotransmitter or neuromodulator within two dif ferent brain regions to produce satiety - one region which includes the nuc leus tractus solitarius in the hindbrain, and another more distributed regi on within the medial-basal hypothalamus. (C) 2000 Elsevier Science B.V. All rights reserved.