Molecular Brain Research 113 (2003) 133–138 www.elsevier.com / locate / molbrainres Short communication Fasting activates neuropeptide Y neurons in the arcuate nucleus and the paraventricular nucleus in the rhesus macaque a, a,b a a * Kevin L. Grove , Peilin Chen , Frank H. Koegler , Andrew Schiffmaker , a,b a,b M. Susan Smith , Judy L. Cameron a Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR 97006-5384, USA b Department of Physiology and Pharmacology, Oregon Health and Science University, Portland, OR 97239, USA Accepted 3 March 2003 Abstract It is well accepted that neuropeptide Y (NPY) plays a pivotal role in the regulation of food intake and energy homeostasis in the rodent, with NPY neurons in the arcuate nucleus (ARH) being thought of as the major contributor to the complex central feeding circuitry. Recent data from our group also indicate that NPY is important in the regulation of energy homeostasis in the nonhuman primate (NHP); exogenous NPY administration into the 3rd ventricle is a potent stimulator of food intake in the male rhesus macaque. The purpose of this study was to determine if NPY neurons in the rhesus macaque respond to a metabolic challenge, induced by 48 h of fasting, in a manner similar to that seen in the rodent. NPY mRNA was detected in hypothalamic sections from 48-h fasted or fed rhesus monkeys by in situ 35 hybridization, using a [ S]UTP-labeled riboprobe specific for human NPY. Not surprisingly, NPY mRNA was abundant in the ARH of the NHP; however, of great interest was the expression of NPY mRNA in neurons within the paraventricular nucleus of the hypothalamus (PVH) and the supraoptic nucleus (SON). This raised the question as to whether all of these populations of NPY neurons are sensitive to changes in energy availability. Indeed, NPY expression in the ARH and PVH was significantly elevated in response to fasting; however, no significant change was detected in the SON. These data indicate that the NPY neurocircuitry involved in the regulation of food intake is more complex in the NHP than in rodents.  2003 Elsevier Science B.V. All rights reserved. Theme: Endocrine and autonomic regulation Topic: Neuroendocrine regulation: other Keywords: Hypothalamus; PVH; ARH; Feeding; Nonhuman primate; NPY The hypothalamic circuitry that controls appetite and intake and energy balance. Because the ARH has a reduced energy expenditure is complex and involves numerous blood brain barrier, the NPY neurons are in an excellent neurotransmitter and neuropeptide systems, many of which position to sense peripheral signals of energy balance (i.e. function in parallel to either increase or decrease energy leptin, insulin and ghrelin) and transmit that signal to other availability (see reviews: Refs. [17,20,22,25,27]). How- important feeding centers (i.e. paraventricular nucleus of ever, the neuropeptide Y (NPY) system is considered as the hypothalamus, PVH). one of the most abundant and potent modulators of energy Our group has previously demonstrated that many of the homeostasis in the rodent brain. In the normal adult rodent, neuronal systems that have been described as potent NPY neurons in the arcuate nucleus (ARH) are the major modulators of food intake in the rodent are also critical in source of NPY that is involved in the regulation of food the regulation of feeding in the nonhuman primate (NHP). These include a-melanocyte stimulating hormone ( aMSH) and agouti related protein (AGRP) [12], modulators of *Corresponding author. Tel.: 11-503-690-5380; fax: 11-503-690- MC3 / 4 receptors, leptin [24] and NPY [15]. In fact, doses 5384. E-mail address: grovek@ohsu.edu (K.L. Grove). of NPY (1 mg) that stimulate feeding in rodents [4,23] are 0169-328X / 03 / $ – see front matter  2003 Elsevier Science B.V. All rights reserved. doi:10.1016 / S0169-328X(03)00093-7