Regulation of Cholecystokinin Receptors in the Hypothalamus of the Rat: Reciprocal Changes in Magnocellular Nuclei Induced by Food Deprivation and Dehydration

Cholecystokinin (CCK) has been suggested to mediate satiety in a number of non-primate species via its peripheral actions as well as a possible central mechanism involving magnocellular and parvocellular oxytocin release. Quantitative in vitro autoradiography employing [¹²⁵l]-Bolton-Hunter labelled CCK-8S ([¹²⁵I]-CCK-8S) was used to examine the distribution and density of CCK receptors in sections of brain from normal rats and rats deprived of food, water or both food and water for 4 days. In food-deprived rats, specific [¹²⁵I]-CCK-8S binding was reduced by 64 ± 5% in the hypothalamic supraoptic nucleus (SON) and by 44±13% in the paraventricular nucleus of the hypothalamus (PVN). In contrast, water deprivation increased binding of [¹²⁵I]-CCK-8S by 128±15% in the SON and by 196 ± 24% in the PVN, while combined food and water deprivation produced smaller increases in both nuclei (30 ± 5% and 98 ± 26% in SON and PVN respectively). Changes in receptor density in the PVN appeared to be most prominent in the magnocellular (especially oxytocin-rich) subdivisions. None of the treatments employed produced changes in [¹²⁵I]-CCK-8S binding in the ventromedial hypothalamic nucleus or the reticular thalamic nucleus. Both CCK-A and CCK-B receptor subtypes were visualized in the nucleus of the solitary tract and the area postrema of normal rats, but levels of binding to both of these subtypes were unaffected by the experimental treatments. These selective alterations demonstrate the plasticity of CCK receptors in the SON and PVN, and are probably associated with changes in the level of neurochemical activity of magnocellular oxytocinergic neurones in these areas. These results, together with reports of changes in the level of CCK synthesis in cells of the SON and PVN after hyperosmotic stimuli, suggest that CCK may act in an autocrine fashion on these neurones and that both CCK receptors and peptide levels are altered in the same direction following cellular activation or inhibition.