Orexin A Stimulates Hypothalamic–Pituitary–Adrenal (HPA) Axis Function, but not Food Intake, in the Absence of Full Hypothalamic NPY-ergic Activity.

Neonatal monosodium <CSMALL>l<CSMALL>-glutamate (MSG) treatment destroys hypothalamic arcuate nucleus neuronal bodies, thus inducing several metabolic abnormalities. As a result, rats develop a phenotype characterized by hyper-leptinemia and by impaired NPY but normal prepro-orexin hypothalamic mRNAs expression. Thus, our study was designed to explore whether hypothalamic effects of orexin A on food intake and glucocorticoid production develop in the absence of full hypothalamic NPY-ergic activity. For this purpose we evaluated, in control and MSG-treated rats, the consequences of intracerebroventricular (icv) orexin A administration on food intake and changes in circulating levels of ACTH and glucocorticoid. Our results indicate that orexin A icv treatment stimulated hypothalamic–pituitary–adrenal (HPA) axis activity in both MSG-damaged and normal animals, with this response even more pronounced in neurotoxin-damaged rats. Conversely, food intake was only enhanced by icv orexin A injection in normal rats. Our study further supports that acute hypothalamic effects of orexin A on food intake and glucocor-ticoid production are due to independent neuronal sys- tems. While intact arcuate nucleus activity is needed for the orexinergic effect induced by icv orexin A admin-istration, conversely, orexin A–stimulated HPA axis func-tion takes place even in the absence of full NPY-ergic activity. [ABSTRACT FROM AUTHOR]