Sympathetic and hyperthermic reactions by orexin A: Role of cerebral catecholaminergic neurons M. Monda a, ⁎ , An. Viggiano a , Al. Viggiano a , E. Viggiano a , G. Messina a , D. Tafuri b , V. De Luca a a Department of Experimental Medicine, Section of Human Physiology, Second University of Naples, via Costantinopoli 16, 80138 Naples, Italy b Motor Sciences, University of Naples “Pathernope”, Naples, Italy Received 30 May 2006; received in revised form 19 September 2006; accepted 3 October 2006 Available online 28 November 2006 Abstract This experiment tested the effect of a lesion of cerebral catecholaminergic neurons on the sympathetic and thermogenic effects induced by an intracerebroventicular (icv) injection of orexin A. The firing rates of the sympathetic nerves to the interscapular brown adipose tissue (IBAT), along with IBAT, colonic temperatures and heart rate were monitored in urethane-anesthetized male Sprague–Dawley rats before an injection of orexin A (1.5 nmol) into the lateral cerebral ventricle and over a period of 150 min after the injection. Three days before the experiment, the rats were pre-treated with an icv injection of 6-hydroxydopamine (6-OHDA) or 6-OHDA plus desipramine or saline. The results show that orexin A increases the sympathetic firing rate, IBAT, colonic temperatures and heart rate in the rats pre-treated with saline. This increase is blocked by the pre-treatment with 6-OHDA alone or 6-OHDA plus desipramine. These findings indicate that cerebral catecholaminergic neurons (particularly the dopaminergic pathway) play a fundamental role in the complex reactions related to activation of the orexinergic system. © 2006 Elsevier B.V. All rights reserved. Keywords: Autonomic nervous system; Rat; Thermoregulation 1. Introduction An intracerebroventricular (icv) injection of the hypotha- lamic neuropeptide “orexin A” is able to induce multiform reactions, as expression of generalized activation of sympa- thetic nervous system. Although this neuropeptide is named for its influence on food intake [25], an icv injection of orexin A does not merely affect eating behavior. Rather it also induces an increase in heart rate [19], blood pressure [23] and metabolic rate [12], indicating that this neuropeptide plays a role in the control of vegetative functions [1]. Orexin A also influences body temperature. In fact, an icv administration of orexin A induces an increase in the firing rate of the sympa- thetic nerves to interscapular brown adipose tissue (IBAT), accompanied with a rise in IBAT and colonic temperatures [17]. In addition, the presence of orexin receptors in many cerebral areas suggests that additional functions are played by orexin A [11,13]. A role for the orexins in sleep regulation has been demonstrated [2]. A deficiency in orexin neurotransmis- sion results in the sleep disorder narcolepsy in mice, dogs, and humans [27]. Some antipsychotic drugs are capable of modifying the re- actions due to the icv injection of orexin A. An administration of haloperidol or clozapine respectively reduces or blocks these reactions [15,16], while risperidone increases sympathetic and hyperthermic reactions induced by orexin A in the rat [18]. Since these psycho-active substances influence both dopami- nergic and noradrenergic cerebral pathways, the aim of this study was to investigate the role of these pathways in reactions due to an icv injection of orexin A, by destroying both pathways with 6-hydroxydopamine (6-OHDA) or a dopaminergic path- way alone with 6-OHDA plus desipramine [7]. Regulatory Peptides 139 (2007) 39 – 44 www.elsevier.com/locate/regpep ⁎ Corresponding author. Dipartimento di Medicina Sperimentale, Sezione di Fisiologia Umana, Seconda Università di Napoli, Via Costantinopoli 16, 80138 Napoli, Italy. Tel.: +39 81 566 5823; fax: +39 81 5667500. E-mail address: marcellino.monda@unina2.it (M. Monda). 0167-0115/$ - see front matter © 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.regpep.2006.10.002