Neuropeptide Y (NPY) and agouti gene-related
protein (AGRP) are orexigenic
peptides of special importance for control of food intake. In situ hybridization studies have shown that NPY and AGRP mRNAs are increased in the arcuate nucleus of the hypothalamus (
ARC) by glucoprivation. Other work has shown that glucoprivation stimulates food intake by activation of hindbrain glucoreceptor cells and requires the participation of rostrally projecting
norepinephrine (NE) or
epinephrine (E) neurons. Here we determine the role of hindbrain
catecholamine afferents in glucoprivation-induced increase in
ARC NPY and AGRP gene expression. The selective NE/E
immunotoxin saporin-conjugated antidopamine-beta-
hydroxylase (anti-dbetah) was microinjected into the medial hypothalamus and expression of AGRP and NPY
mRNA was analyzed subsequently in the
ARC under basal and glucoprivic conditions using (33)P-labeled in situ hybridization.
Saporin-conjugated anti-dbetah virtually eliminated dbetah-immunoreactive terminals in the
ARC without causing nonspecific damage. These lesions significantly increased basal but eliminated 2-deoxy-D-glucose-induced increases in AGRP and NPY
mRNA expression. Results indicate that hindbrain catecholaminergic neurons contribute to basal NPY and AGRP gene expression and mediate the responsiveness of NPY and AGRP neurons to
glucose deficit. Our results also suggest that
catecholamine neurons couple potent orexigenic neural circuitry within the hypothalamus with hindbrain
glucose sensors that monitor brain
glucose supply.