Several types of endogenous opioid peptides stimulate food intake, and opioid receptor blockade reduces intake. It has therefore been proposed that opioids play a role in the regulation of feeding. Manipulation of certain aspects of this opioid feeding system may be a safe and effective method of treating human feeding disorders such as anorexia, bulimia, and some types of obesity. The proposed work will attempt to characterize this opioid system in terms of the specific peptides involved and their neural sites of action. Initial work will systematically compare the feeding effects of the microinfusions of three opioids with different receptor selectivities: Beta-endorphin, dynorphin-1-17 and D-ala2-D-leu5-enkephalin. The peptides will be injected into several different brain sites in an effort to determine their primary sites of action. Where feeding effects are noted, dose response relationships will be developed. A careful measure of meal parameters and other behaviors will give some indication of the behavioral specificity of the opioids. In another set of experiments, microinjections will be used to """"""""map"""""""" brain areas in which naloxone acts to reduce food intake. This effect of naloxone presumably reflects the blockade of endogenous opioid activity, and the effective brain sites should, in most cases, be those into which injections of opioids stimulate feeding. A final set of experiments will confirm the importance of certain brain sites in mediating opioid feeding effects by demonstrating that lesions in these brain areas attenuate or abolish the opioid effects. The proposed studies will contribute new information about the initiation of feeding that will complement the large body of literature that exists on the termination of feeding.
| Gosnell, B A; Grace, M; Billington, C J et al. (1989) Effects of streptozotocin-induced diabetes on feeding stimulated by centrally administered opioid agonists. Life Sci 45:31-40 |
| Gosnell, B A (1988) Involvement of mu opioid receptors in the amygdala in the control of feeding. Neuropharmacology 27:319-26 |
| Gosnell, B A (1987) Central structures involved in opioid-induced feeding. Fed Proc 46:163-7 |
| Gosnell, B A (1987) Effects of dietary dehydroepiandrosterone on food intake and body weight in rats with medial hypothalamic knife cuts. Physiol Behav 39:687-91 |
| Gosnell, B A; Grace, M; Levine, A S (1987) Effects of beta-chlornaltrexamine on food intake, body weight and opioid-induced feeding. Life Sci 40:1459-67 |
| Morley, J E; Levine, A S; Gosnell, B A et al. (1987) Effect of neuropeptide Y on ingestive behaviors in the rat. Am J Physiol 252:R599-609 |
| Gosnell, B A; Lipton, J M (1986) Opioid peptide effects on feeding in rabbits. Peptides 7:745-7 |
