Blockers of nitric oxide synthase inhibit stress activation of c-fos expression in neurons of the hypothalamic paraventricular nucleus in the rat

Abstract

The cellular transcription factor Fos, product of the immediate early gene c-fos, is induced in secretory neurons of the hypothalamic paraventricular nucleus in response to stress. Recent evidence indicates that the paracrine-acting messenger molecule nitric oxide may be involved in the activation or regulation of c-fos expression in neurons, and many neurons in the paraventricular nucleus contain the enzyme nitric oxide synthase. Furthermore, nitric oxide has been implicated in the regulation of corticotropin-releasing factor and arginine vasopressin release from neurons of the paraventricular nucleus. To study whether nitric oxide is involved in stress activation of c-fos expression in the paraventricular nucleus, we assessed the effect of treatment with competitive nitric oxide synthase blockers on expression of Fos protein in neurons of the paraventricular nucleus of rats subjected to immobilization stress. We found that such treatment blocks stress-induced Fos expression in the paraventricular nucleus. Furthermore, using double staining for Fos and the nitric oxide synthase histochemical marker, nicotinamide adenine dinucleotide phosphatediaphorase, we found that many neurons in the paraventricular nucleus that express Fos in response to immobilization stress also contain nitric oxide synthase. These results indicate that nitric oxide is involved in the regulation of Fos expression in stress-activated cells of the paraventricular nucleus.