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Endocrinology Vol. 142, No. 3 1050-1056
Copyright © 2001 by The Endocrine Society

ARTICLES

Immediate and Prolonged Patterns of Agouti-Related Peptide-(83–132)-Induced c-Fos Activation in Hypothalamic and Extrahypothalamic Sites1

Mary M. Hagan, Stephen C. Benoit, Paul A. Rushing, Laurel M. Pritchard, Stephen C. Woods and Randy J. Seeley

Department of Psychology (M.M.H.), University of Alabama, Birmingham, Alabama 35294-1170; Department of Psychiatry, University of Cincinnati Medical Center (S.C.B., P.A.R., L.M.P., S.C.W., R.J.S.), Cincinnati, Ohio 45267-0559

Address all correspondence and requests for reprints to: Mary M. Hagan, Ph.D., 415 Campbell Hall, Department of Psychology, University of Alabama, Birmingham, Alabama 35294-1170. E-mail: mhagan{at}uab.edu

Several lines of evidence substantiate the important role of the central nervous system melanocortin 3- and 4-receptor (MC3/4-R) system in the control of food intake and energy balance. Agouti-related peptide (AgRP), an endogenous antagonist of these receptors, produces a robust and unique pattern of increased food intake that lasts up to 7 days after a single injection. Little is known about brain regions that may mediate this powerful effect of AgRP on food intake. To this end we compared c-Fos-like immunoreactivity (c-FLI) in several brain sites of rats injected intracerebroventricularly with 1 nmol AgRP-(83–132) 2 and 24 h before death and compared c-FLI patterns to those induced by another potent orexigenic peptide, neuropeptide Y (NPY). Although both NPY and AgRP induced c-FLI in hypothalamic areas, AgRP also produced increased c-FLI in the accumbens shell and lateral septum. Although NPY elicited no changes in c-FLI 24 h after administration, AgRP induced c-FLI in the accumbens shell, nucleus of the solitary tract, central amygdala, and lateral hypothalamus. These results indicate that an NPY-like hypothalamic circuit mediates the short-term effects of AgRP, but that the unique sustained effect of AgRP on food intake involves a complex circuit of key extrahypothalamic reward and feeding regulatory nuclei.




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