BRAIN RESEARCH ELSEVIER Brain Research 660 (1994) 96-103 Research report Hormonal and metabolic effects of paraventricular hypothalamic administration of neuropeptide Y during restand feeding Gertjan van Dijk *, Antonio E. Bottone, Jan H. Strubbe, Anton B. Steffens Department of Animal Physiology, University of Gronmgen, PO Box 14, 9750 AA Haren, The Netherlands Accepted 19 July 1994 Abstract To investigate the role of neuropeptide Y (NPY) in the paraventricular nucleus of the hypothalamus (PVN) in the regulation of autonomic outflow, hormonal (plasma insulin and catecholamines), metabolic (blood glucose and plasma free fatty acids) and cardiovascular (heart rate and main arterial pressure) indices were measured before, during, and after bilateral infusion of NPY (1.0, 0.2, 0.04/zg in 1 /zl synthetic CSF) into the PVN of conscious resting rats. Administration of the highest dose (1,0/~g//zl) caused bradycardia and reduced circulating norepinephrine levels without effecting circulating fuels, insulin or epinephrine. In a second experiment, feeding-induced changes in hormonal and metabolic indices were assessed after NPY administration (1.0 /xg//zl) into the PVN. During and after feeding, NPY enhanced the feeding-induced insulin response (P < 0.01) and attenuated the feeding-induced norepinephrine response (P < 0.05). The results of the present study suggest that stimulation of NPY receptors in the PVN decreases sympathetic activity and increases parasympathetic activity in resting conditions, and that these effects are potentiated during feeding. Keywords: Neuropeptide Y; Paraventricular nucleus; Autonomic outflow; Food intake; Cardiovascular regulation; Insulin; Norepinephrine; Nutrient storage 1. Introduction There is considerable evidence that neuropeptide Y (NPY)-containing neurons in the hypothalamus are involved in the integration of feeding behavior, fuel homeostasis, and cardiovascular regulation (for reviews see [3,6,21,34,47]). It is known that administration of NPY into hypothalamic areas, in particular the subfor- nical and paraventricular areas (PVN), has profound orexigenic properties [38-40]. Furthermore, adminis- tration of NPY into the PVN influences peripheral energy metabolism [25], modulates pancreatic hormone secretion [1,26], decreases sympathetic nerve activity in brown adipose tissue [7], and reduces cardiovascular responsiveness [12,13]. Moreover, it stimulates the pitu- itary-adrenocortical axis [45]. In combination with neu- roanatomical data [11], the aforementioned findings suggest that NPY receptors within the area of the PVN are involved in regulation of autonomic outflow; i.e., * Corresponding author. Fax: (3l) (50) 635205. 0006-8993/94/$07.00 © 1994 Elsevier Science B.V. All rights reserved SSDI 0006-8993(94)00906-6 the activities of the parasympathetic and sympathetic divisions of the autonomic nervous system. Both divi- sions of the autonomic nervous system play an impor- tant role in the regulation of fuel homeostasis and cardiovascular processes [10,28]. Under baseline metabolic (i.e., resting and prepran- dial) conditions the activity of both divisions of the autonomic nervous system is rather low. This is indi- cated by low circulating catecholamine levels for the sympathetic nervous system [9,18], and a low parasym- pathetic activity under these conditions can be inferred from low firing frequency in vagal hepatic and pancre- atic nerves [28] and from the low insulin and PP levels which are partly under parasympathetic control [15]. Since the activity of several hypothalamic areas is rela- tively low under basal resting conditions, manipulation of these hypothalamic areas might result in minor alterations in autonomic outflow. Accordingly, under non-basal arousal conditions manipulation of hypotha- lamic areas, in particular the PVN which projects to the motor-neuron pools of the sympathetic and para- sympathetic system [22], may result in profound changes