Regulatory Peptides 95 (2000) 109–113 www.elsevier.com / locate / regpep Involvement of neuropeptide Y and Y1 receptor in antinociception in nucleus raphe magnus of rats a b a,b, * Yu-Xuan Zhang , Thomas Lundeberg , Long-Chuan Yu a Department of Physiology, College of Life Sciences, Peking University, Beijing 100871, China b Department of Physiology and Pharmacology, and Department of Medical Rehabilitation, Karolinska Institutet, 171 77 Stockholm, Sweden Received 28 May 2000; received in revised form 10 July 2000; accepted 17 July 2000 Abstract The nociceptive response latencies increased significantly after intra-nucleus raphe magnus administration of 0.1 or 0.4 nmol of neuropeptide Y, but not 0.04 nmol, in rats. The neuropeptide Y-induced increases in hindpaw withdrawal latency were reversed by following injection of 0.42 nmol of the Y1 antagonist, NPY(28–36). The results indicate that NPY plays an antinociceptive role in nucleus raphe magnus in rats, which is mediated by the Y1 receptor. Furthermore, the neuropeptide Y-induced increases in hindpaw withdrawal latency were attenuated by following intra-nucleus raphe magnus injection of 6 nmol of the opioid antagonist naloxone, indicating that there is an interaction between NPY and opioids in nucleus raphe magnus.  2000 Elsevier Science B.V. All rights reserved. Keywords: Nucleus raphe magnus (NRM); Neuropeptide Y; Y1 receptor; Naloxone; Hindpaw withdrawal latency (HWL); Antinociceptive effect 1. Introduction stations in the descending pathway of analgesia, periaqueductal grey (PAG) and the nucleus raphe magnus Neuropeptide Y (NPY) and its receptors distribute (NRM) [8–11]. It has been reported that there is a widely in the mammalian central and peripheral nervous connection between periaqueductal grey and NRM [9,10]. system [1–4]. Many studies have demonstrated that the The main descending pathway is from PAG to NRM, then NPY may be involved in the mechanisms of endogenous going through the dorsal longitudinal tract to dorsal horn antinociceptive system [5–7]. Recent study in our labora- of the spinal cord [9,10]. Many neurotransmitters and tory demonstrated that intra-periaqueductal grey (PAG) neuropeptides co-exist in the descending analgesic path- injection of NPY resulted in a dose-dependent antinocicep- ways from periaqueductal grey and NRM to the dorsal tive effect in rats, and the effect was blocked by following horn of the spinal cord, that include serotonin, enkephalin, intra-PAG injection of the Y1 receptor antagonist NPY28– substance P, somatostatin, galanin, vasoactive intestinal 36. Furthermore, the NPY-induced increases in hindpaw polypeptide, neuropeptide Y and calcitonin gene-related withdrawal latency were attenuated by the opioid antago- peptide (CGRP) [10,12–14]. The present study was per- nist naloxone. The results indicated that NPY plays an formed to investigate the anti-nociceptive effect of NPY in antinociceptive role in PAG of rats, and there is an NRM and the possible interaction between NPY and interaction between NPY and opioids in PAG [7]. opioids in NRM of rats. Descending pathways of analgesia from midbrain to dorsal horn of the spinal cord play a crucial role on the 2. Materials and methods transmission of nociceptive information from the periphery to central nervous system. There are two major relay 2.1. Animals All experiments were performed on freely moving male *Corresponding author. Tel.: 86-10-6275-1867; fax: 86-10-6275-1526. E-mail address: yulc@pku.edu.cn (L.-C. Yu). Sprague–Dawley rats weighing from 200 to 300 g (Ex- 0167-0115 / 00 / $ – see front matter  2000 Elsevier Science B.V. All rights reserved. PII: S0167-0115(00)00165-8