Chronic nicotine treatment (4 mg/kg per day; 14 days) significantly reduced
the affinity and density of orexin-A binding sites in the anterior hypotha
lamus of rat brain. There was a significantly lower sensitivity of orexin-A
binding to orexin peptides, to the related secretin and pituitary adenylat
e cyclase activating peptide, and to unrelated neuropeptide Y (NPY). This c
hange correlated with selective downregulation of a fraction of hypothalami
c NPY Y-1 receptors. In previous studies, we have demonstrated an increase
in the levels of orexin-A peptide and NPY in discrete hypothalamic areas up
on nicotine treatment. This finding contradicts an expected increase in the
production of these orexigenic peptides in a model where an inverse relati
onship is observed between food consumption and nicotine treatment. This st
udy provides a possible explanation to this inconsistency in that a decreas
e in affinity of orexin-A binding could reduce neural orexin signaling, whi
ch may contribute to decreased food intake observed in smokers and animals
chronically treated with nicotine. (C) 2001 Published by Elsevier Science I
reland Ltd.