In humans, exposure to moderate levels of lead (Pb) causes a reduction in birth weight and postnatal growth. We have determined that in the postweaning Pb-exposed rat, the growth-depressive action of Pb can be accounted for by depression of food consumption, with no change in efficiency of food utilization. In the face of hyperalimentation, the Pb-exposed rat down-regulates its spontaneous food consumption in proportion to the caloric supplement forced upon it, thus maintaining its caloric intake at the level which preceded supplementation. Thus it appears that (as with certain experimental hypothalamic lesions and TCDD exposure) the """"""""set-point"""""""" for growth is lowered.
The aim of the proposed study is to more thoroughly characterize the actions of Pb exposure on appetite, particularly with respect to: a) the critical age, or period of neuronal development, at which Pb impacts on postweaning food intake, b) the reversibility of Pb-induced growth/appetite depression, and c) the role of specific neuronal/hormonal processes as determinants of the degree of appetite depression induced by Pb. In this last respect, it is proposed to undertake studies regarding the role of prolactin (PRL) and cholecystokinin (CCK) in Pb-induced depression of appetite. Previous studies have shown that the serum level of PRL is elevated in rats and humans following Pb exposure. An elevation of serum PRL accompanies a) satiety (meal termination) in man, and b) the depression of food consumption and growth in animals which results from ablation of the dorsomedial nucleus of the hypothalamus. Systemic administration of CCK produces an elevation in PRL, and there is evidence that CCK serves as a meal-terminating satiety signal. Since CCK receptors are located in both the gut and in the CNS, the potential differential effects on food intake we have observed following orally vs. systemically administered Pb may be explained by separate, additive effects of Pb on these two populations of CCK receptors. In addition, the influence of Pb on consummatory behavior responses to both feeding initiators and to inducers of satiety will be studied. In all studies involving modulators of food consumption, patterns of initiation, duration, and termination of food intake will be continuously monitored using a computerized system.
