HISTAMINE STIMULATES C-FOS EXPRESSION IN HYPOTHALAMIC VASOPRESSIN-RELEASING, OXYTOCIN-RELEASING, AND CORTICOTROPIN-RELEASING HORMONE-CONTAINING NEURONS

The stimulatory action of centrally administered histamine (HA) on sec retion of the anterior pituitary hormones ACTH, beta-endorphin, and PR L is indirect, and previous studies have suggested that hypothalamic n eurons containing CRH, arginine vasopressin (AVP), and oxytocin (OT) a re involved in this response. We studied the effect of HA on neuronal activation in the hypothalamus by investigating the expression of c-fo s, which is a protooncogene activated early when neurons are stimulate d. The expression of c-fos was evaluated by detection of c-fos immunor eactivity (c-fos-IR) using immunohistochemistry and by measurement of c-fos mRNA using in situ hybridization techniques. In addition, the id entity of the HA-stimulated neurons was investigated by dual antigen i mmunohistochemistry visualizing AVP-, OT-, or CRH-IR in the neurons sh owing increased c-fos expression. HA (270 nmol) infused intracerebrove ntricularly increased c-fos-IR in the hypothalamus, especially in the periventricular hypothalamic areas and certain hypothalamic nuclei, in cluding the paraventricular nucleus (PVN) and supraoptic nucleus (SON) , c-fos-immunoreactive nuclei were observed throughout the SON, wherea s in the PVN, c-fos IR was particularly pronounced in the subnuclei kn own to contain AVP, OT, and CRH neurons. Double labeling experiments c onfirmed that c-fos was expressed in AVP-, OT-, and CRH-immunoreactive as well as other neurons. In addition, HA intracerebroventricularly i nduced a moderate expression of c-fos-IR in the arcuate nucleus. In si tu hybridization showed increased levels of c-fos mRNA in both the PVN and SON after HA infusion. We conclude that HA-induced secretion of A CTH, beta-endorphin, and PRL may be mediated via activation of hypotha lamic AVP, OT, and CRH neurons.