Neurally active peptides, originating in central neurons (neuropeptides) or in gut and endocrine tissues, are potent participants in the physiological control of motivated behaviors. My research has focused on peptide neurotransmitters/hormones and their receptors implicated in energy balance, control of food intake and the regulation of body weight. One of these peptides, neuropeptide Y (NPY), is a neurotransmitter with a widespread and abundant distribution in the CNS. Most attention given to NPY’s role in feeding has focused on its central action in the hypothalamus where a single injection of NPY stimulates dramatic overeating, and repeated injections result in obesity. However, we have shown that the hindbrain may also be a target of NPY’s action in feeding. Moreover, we have identified NPY receptor subtypes in the dorsal pons which exhibit profiles of agonist binding consistent with the profile of agonist potency to stimulate feeding. Preliminary results also show that microinjection of NPY into the dorsal pons stimulates food intake. Taken together, these results raise the possibility that NPY activity at synapses in the dorsal pons influences neural pathways involved in the stimulation of feeding; pathways that might, for example, be recruited in the compensatory increase in food intake that follows a fast.

Eric S. Corp  Neuropeptides and Motivated Behavior: Neuroendocrine Controls of Feeding and Reproductive Behavior Thus, the hindbrain NPY system may be part of a larger neural network controlling food intake. In ongoing studies, we are pursuing this hypothesis, and further characterizing the hindbrain NPY system involved in feeding, energy balance and body weight regulation, through a combination of neuroanatomical and behavioral approaches, which include receptor autoradiography, site-specific microinjection of selective agonists and antagonists, immunocytochemistry and neural tract tracing. Energy balance, in humans and rodents, has a direct impact on the neuroendocrine axis and reproductive capacity. With George N. Wade, we are examining the relationship between NPY and the behavioral aspects of nutritional infertility. These studies show that a single injection of NPY or an NPY receptor selective agonist, given into the lateral cerebral ventricle of ovariectomized steroid-primed hamsters, will block estrous behavior (lordosis) for 5 hrs or longer. Moreover, different NPY receptor subtypes are involved in different behaviors. That is, NPY-Y5 receptors appear to mediate NPY effects on lordosis while NPY-Y1 and NPY-Y2 receptors are involved in mediating stimulatory effects of NPY on food intake. Localizing the different loci where NPY acts to influence these distinct behaviors, and tracing back the origin of NPY projections to these loci, are two continuing aims of this project. NPY is only one of several peptides that appear to play a role in feeding or reproduction, or both. Also under experimental consideration are leptin, a protein secreted by adipose tissue and carried by the blood to targets in the brain, and cholecystokinin-8, a neuro- and gut-endocrine peptide with both peripheral and central actions. Both these neurally active peptides have functional roles in both feeding and reproductive behavior.

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Publications:

Fitts DA, Corp ES, Simpson JB (1982) Salt appetite and intravascular volume depletion following colloid dialysis in hamsters. Behav Neural Biol 34: 75-88.

Fitts DA, Yang O, Corp ES, Simpson JB (1983) Sodium retention following DOCA in hamsters. Am J Physiol 244: R78-83.

Baskin DG, Brewitt B, Corp ES, Davidson D, Paquette T, Figlewicz DP, Porte Jr D, Dorsa DM (1986) Quantitative autoradiographic evidence for insulin receptors in the choroid plexus of the rat brain. Diabetes 35: 246-249.

Baskin DG, Davidson D, Corp ES, Lewellen T, Graham M (1986) An inexpensive micorcomputer digital imaging system for densitometry: quantitative autoradiography of insulin receptors with [¹²⁵I]-insulin and LKB film. J Neurosci Meth 16: 119-129.

Bohannon NJ, Figlewicz DP, Corp ES, Wilcox BJ, Porte Jr D, Baskin DG (1986) Identification of binding sites for an insulin-like growth factor (IGF-1) in the median eminence of the rat brain by quantitative autoradiography. Endocrinology 119: 943-945.

Corp ES, Woods SC, Porte Jr D, Figlewicz DP, Dorsa DM, Baskin DG (1986) Localization of [¹²⁵I]-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci Lett 70: 17-22.

Bohannon NJ, Corp ES, Wilcox BJ, Figlewicz DP, Dorsa DM, Baskin DG (1988) Characterization of insulin-like growth factor-1 (IGF-1) receptors in the median eminence of the brain and their modulation by food restriction. Endocrinology, Suppl.122: 1940-1947.

Bohannon NJ, Corp ES, Wilcox BJ, Figlewicz DP, Dorsa DM, Baskin DG (1988) Localization of binding sites for insulin-like growth factor-1 (IGF-1) in the rat brain by quantitative autoradiography. Brain Res 444: 205-213.

Wilcox BJ, Corp ES, Dorsa DM, Figlewicz DP, Greenwood MRC, Woods SC, Baskin DG (1989) Insulin binding in the hypothalamus of lean and genetically obese Zucker rats. Peptides 10: 1159-1164.

Corp ES, Melville LD, Greenberg D, Gibbs J, Smith GP (1990) Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors. Am J Physiol 259: R317-R323.

Davidson DA, Bohannon NJ, Corp ES, Lattemann DP, Woods SC, Porte Jr D, Dorsa DM, Baskin DG (1990) Evidence for separate receptors for insulin and insulin-like growth factor-I in choroid plexus of rat brain by quantitative autoradiography. J Histochem Cytochem 38: 1289-1294.

Corp ES, Smith GP (1991) Characterization of axonally transported [¹²⁵I] PYY binding sites in rat vagus nerve. Brain Res 553: 175-179.

Weller A, Corp ES, Tyrka A, Ritter RC, Brenner L, Gibbs J, Smith GP (1992) Trypsin inhibitor and maternal reunion increase plasma cholecystokinin in neonatal rats. Peptides 13: 939-941.

Corwin RL, Corp ES, Gibbs J, Smith GP (1992) Decreased behavioral effects of daily intracerebroventricular bombesin. Peptides 13: 1215-1218.

Corp ES, McQuade J, Moran TH, Smith GP (1993) Characterization of type A and type B cholecystokinin receptor binding sites in rat vagus nerve. Brain Res 623: 161-166.

Turner M, Corp ES Galbraith RA (1994) Inhibition of the feeding response to NPY in cobalt protoporphyrin-treated rats is a post-receptor defect. Physiol Behav 56: 1009-1014.

Geary N, Smith GP, Corp ES (1996) The increased satiating potency of CCK-8 is not mediated by upregulation of NTS CCK receptors. Brain Res 179: 179-186.

Min N, Joh TH, Corp ES, Baker H, Cubells JF, Son JH (1996) A transgenic mouse model to study trans-synaptic regulation of tyrosine hydroxylase gene expression. J Neurochem 67: 11-18.

Corp ES (1996) The receptor bases of neuropeptide Y-induced food intake. In: Drug Receptor Subtypes and Ingestion. Cooper SJ, Clifton PG, eds., Academic Press, London, pp. 323-345.

Corp ES, Curcio M, Gibbs J, Smith GP (1997) The effect of centrally administered CCK receptor antagonists on food intake in rats. Physiol Behav 61: 823-827.

Houpt TA, Corp ES, Berlin RA (1998) Intracerebroventricular angiotensin II stimulates intraoral intake of water in rats. Peptides 19: 171-173.

Corp ES, Conze DB, Smith F, Campfield LA (1997) Regional localization of specific [¹²⁵I] leptin binding sites in rat forebrain. Brain Res 789: 40-47.

Asarian L, Corp ES, Hrupka B, Geary N (1998) Intracerebroventicular GLP-1 inhibits sham feeding in rats without eliciting satiety. Physiol Behav 64: 367-72.

Corp, E.S., McQuade, J., Krasnicki, S., Conze, D.B. Feeding after fourth ventricular administration of neuropeptide Y receptor agonists, Peptides (in press).

Corp, E.S., Greco, B., Powers, J.B., Marin Bivens, C., Wade, G. Neuropeptide Y inhibits estrous behavior and stimulates food intake through separate receptors in Syrian hamsters, Am J. Physiol. (in revision).

Jones, J.E., Corp, E.S., Wade, G.N. Effects of naltrexone and CCK on estrous behavior and food intake in Syrian hamsters, Peptides (in revision).

 

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