Impact of food deprivation on α1- and α2-noradrenergic receptors in the paraventricular nucleus and other hypothalamic areas

Abstract

Hypothalamic norepinephrine may modulate normal eating behavior through activation of α 2-noradrenergic receptors, localized in the paraventrieular nucleus (PVN). We investigated whether these receptors, which stimulate food ingestion, may in turn be altered by the nutritional state of the organism. Thus the impact of food deprivation, on the specific binding of [3H]-paminoclonidine ([3H]PAC) to α 2-noradrenergic receptors in discrete hypothalamic areas, was examined in rats. The results of our first experiment revealed that 48 hr food deprivation reduced (by 50%) the maximum number of binding sites (Bmax) of the high affinity component of [3H]PAC binding to α 2 receptors. This effect occurred exclusively in the medial hypothalamus (which includes the PVN), without any change in the affinity (Kd) of these receptors. A smaller decline was seen in the low affinity binding sites of the medial hypothalamus, whereas no changes were observed in the density or affinity of the high and low affinity α 1 receptor sites in the lateral hypothalamus or frontal cortex. The α 1-noradrenergic receptor sites, as defined by [3H]prazosin and [3H]WB-4101 binding, were also unaffected in the different brain areas by 48 hr food deprivation. An additional analysis of α 2-receptors in discrete hypothalamic nuclei demonstrated that the deprivationinduced decline in α 2-receptor binding: (1) occurred specifically in the PVN; (2) was apparent after as little as 3 hr food deprivation; and (3) occurred only when this brief deprivation fell at the onset of the dark cycle, as opposed to at the end of the dark cycle. These results reveal once again the relationship of PVN α 2-noradrenergic receptors to eating behavior in the rat, and show that these receptors, believed to control normal food intake, are themselves affected by the rat's nutritional state. From other evidence, it is suggested that blood glucose levels may be important in producing these deprivationinduced changes in hypothalamic α 2 receptors.