The neuropeptide Y agouti gene-related protein (AGRP) brain circuitry in normal, anorectic, and monosodium glutamate-treated mice

Neuropeptide Y (NPY) and the endogenous melanocortin receptor antagonist, a gouti gene-related protein (AGRP), coexist in the arcuate nucleus, and both exert orexigenic effects. The present study aimed primarily at determining the brain distribution of AGRP. AGRP mRNA-expressing cells were limited to the arcuate nucleus, representing a major subpopulation (95%) of the NPY n eurons, which also was confirmed with immunohistochemistry. AGRP-immunoreac tive (-ir) terminals all contained NPY and were observed in many brain regi ons extending from the rostral telencephalon to the pens, including the par abrachial nucleus. NPY-positive, AGRP-negative terminals were observed in m any areas. AGRP-ir terminals were reduced dramatically in ail brain regions of mice treated neonatally with monosodium glutamate as well as of mice ho mozygous for the anorexia mutation. Terminals immunoreactive for the melano cortin peptide alpha-melanocyte-stimulating hormone formed a population sep arate from, but parallel to, the AGRP-ir terminals. Our results show that a rcuate NPY neurons, identified by the presence of AGRP, project more extens ively in the brain than previously known and indicate that the feeding regu latory actions of NPY may extend beyond the hypothalamus.