Rapid and preferential activation of Fos protein in hypocretin/orexin neurons following the reversal of dehydration-anorexia

Abstract

Dehydration (DE)-anorexia is stimulated by chronic consumption of hypertonic saline. Spontaneous nocturnal food intake is markedly reduced with this treatment but is rapidly reversed upon the return of drinking water. Here we examined the neurons in the lateral hypothalamic area (LHA) of chronically dehydrated rats for their peptidergic phenotype, colocalization, and activation profiles following the rapid reversal of anorexia. To do this, we used double-labeling combinations of Fos immunocytochemistry and radioisotopic- and digoxigenin-labeled in situ hybridization. We found that lateral hypothalamic corticotropin-releasing hormone (CRH) neurons show extensive coexpression with neurotensin mRNA, but they are distinct from hypocretin/orexin and melanin-concentrating hormone (MCH) neurons. Chronic dehydration increases Fos-ir in large numbers of neurons in dorsal regions of the LHA. Some of these LHA neurons also show increased CRH, but not hypocretin/orexin or MCH gene expression, as dehydration-anorexia develops. Furthermore, the behavioral sequence of eating and increased activity exhibited by DE animals in the minutes following water drinking is accompanied by a further increase in the number of Fos-ir nuclei in the LHA. Increased Fos activation occurs in a significant number of LHA hypocretin/orexin neurons, but not CRH or MCH neurons, in the LHA. Together these data implicate CRH but not hypocretin/orexin or MCH neurons in the LHA in the motor events associated with dehydration. However, when water is returned, contributions to the network controlling responses evidently come from hypocretin/orexin, but not CRH or MCH, neurons in the LHA.