Immediate and prolonged patterns of Agouti-related peptide-(83--132)-induced c-Fos activation in hypothalamic and extrahypothalamic sites.
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.
Hagan
M M
MM
Department of Psychology, University of Alabama, Birmingham, Alabama 35294-1170, USA. mhagan@uab.edu
Benoit
S C
SC
Rushing
P A
PA
Pritchard
L M
LM
Woods
S C
SC
Seeley
R J
RJ
D054369:Agouti-Related Protein; D000818:Animals; D001921:Brain / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D016760:Proto-Oncogene Proteins c-fos / Q000502:physiology*; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors; D014018:Tissue Distribution / Q000187:drug effects
D054369:Agouti-Related Protein; D009478:Neuropeptide Y; D010446:Peptide Fragments; D016760:Proto-Oncogene Proteins c-fos; C411703:agouti-related protein-(83-132)