Neuroscience Letters 383 (2005) 231–235 The role of norepinephrine and nitric oxide in activities of rat arginine vasopressin neurons in response to immune challenge Shuang Xu a,b,c , Shiyu Guo a,b , Xinhong Jiang a,b , Teruyasu Umezawa a , Tadashi Hisamitsu a,* a Department of Physiology, School of Medicine, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan b Laboratory of Neurobiology, School of Medicine, Soochow University, 48 Renmin Road, Suzhou 215007, PR China c Department of Psychiatry, Center of Pharmacogenomics, Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, 1554A Gonda Center, 695 Charles Young Drive So., Los Angeles, CA 90095-1761 Received 7 February 2005; received in revised form 25 March 2005; accepted 6 April 2005 Abstract To explore the potential role of norepinephrine (NE) and nitric oxide (NO) in activities of rat hypothalamus arginine vasopressin (AVP) neurons in response to immune challenge, we observed the effect of prazosin, an antagonist of  1 -adrenergic receptor, and the specific nitric oxide synthase (NOS) inhibitor N w nitro-l-arginine-methylester (l-NAME) on the Fos expression in AVP neurons induced by systemic lipopolysaccharide (LPS) using double immunohistochemistry. Intravenous (i.v.) injection of LPS induced Fos expression in AVP neurons mainly in the hypothalamus paraventricular nucleus (PVN) and in the supraoptic nucleus (SON). The percentage of Fos-positive AVP neurons was dose-dependent. Pretreatment with prazosin (5 mg/kg) effectively suppressed the Fos expression induced by LPS (5 g/kg), whereas l-NAME (30mg/kg) did not influence the Fos expression in the AVP neurons induced by LPS (0.25, 0.5, 1, 5 g/kg). Our results suggest that the activation of central AVP neurons caused by systemic LPS may be mediated by NE through  1 -adrenergic receptors, but could not be changed by NO. © 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Lipopolysaccharide; Fos; Norepinephrine; Nitric oxide; Arginine vasopressin;  1 -Adrenergic receptor Arginine vasopressin (AVP) is mainly produced in the mag- nocelluar neurons of the paraventricular nucleus (PVN) and supraoptic nucleus (SON) and released into the blood cir- culation from their terminating in the posterior pituitary. AVP is well known to participate in the water conserva- tion, cardiovascular homeostasis. Recent studies show AVP is also involved in the inflammation response. The clinic studies demonstrate that AVP contributes to the maintenance of arterial pressure in the early phase of inflammation and short of AVP caused by depletion of its neurohypophyseal store is an important factor for the hypotension, a typical symptom of the septic shock [16]. Moreover, the animal studies show that systemic administration of lipopolysac- charide (LPS) stimulates the activation of AVP neurons in the hypothalamus and furthermore anti-AVP antiserum ef- fectively inhibits the elevation of ACTH response to IL-1, * Corresponding author. Tel.: +81 3 37848110; fax: +81 3 37845368. E-mail address: tadashi@med.showa-u.ac.jp (T. Hisamitsu). the most important preinflammatory factor [19], suggesting that AVP plays an important role in influencing the activa- tion of hypothalamus–pituitary–adrenal (HPA) response to immune challenges. As LPS cannot stimulate the activation of central neurons directly, some of the mediators could be involved in the neuroendocrine process. Our previous study has indicated that prostaglandins can mediate stimulatory ef- fect of LPS on the activation of hypothalamus AVP neurons [21]. In addition to prostaglandins, norepinephrine (NE) and nitric oxide (NO) could be candidates in the process. Neuroendocrine hypothalamus is abundantly innervated by the noradrenergic projection from the catecholaminergic cell group of the brainstem. These noradrenergic inputs ap- pear to participate in the activation of the HPA axis because systemic administration of IL-1 increases the NE concentra- tion in the hypothalamus [14] and depletion of hypothalamic NE concentrations effectively inhibits the IL-1-induced ele- vation of plasma ACTH or corticosterone [7,14]. Although it is reported that intracerebroventricular (i.c.v.) administration 0304-3940/$ – see front matter © 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.neulet.2005.04.033