TY - JOUR

T1 - Differential roles for neuropeptide Y Y1 and Y5 receptors in anxiety and sedation

AU - Sørensen, Gunnar

AU - Lindberg, Camilla

AU - Wörtwein, Gitta

AU - Bolwig, Tom G

AU - Woldbye, David P D

AU - Sørensen, Gunnar

PY - 2004/9/1

Y1 - 2004/9/1

N2 - Central administration of neuropeptide Y (NPY) causes both anxiolysis and sedation. Previous studies suggest that both effects are mediated via NPY Y1 receptors. However, most of these studies were carried out before the advent of specific NPY receptor ligands. Therefore, a potential role for other NPY receptors in anxiety and sedation remains a possibility. In the present study, we addressed this issue by testing the effects of intracerebroventricular (i.c.v.) injection of NPY as well as specific receptor agonists for the Y1 receptor ([D-His(26)]NPY), Y2 receptor (C2-NPY), and Y5 receptor ([cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]hPP) in the elevated plus maze and open field tests. As with NPY, the Y1 agonist had a dose-dependent anxiolytic-like effect in both behavioral tests. In contrast to NPY, which caused significant sedation in the open field test, the Y1 agonist was without sedative effect. The Y2 agonist showed neither anxiolytic-like nor sedative effects. The Y5 agonist showed anxiolytic-like activity in both behavioral tests and caused sedation in the same dose range as NPY in the open field test. These results indicate that anxiolytic-like effects of i.c.v.-administered NPY in rats are mediated via both Y1 and Y5 receptors, whereas sedation is mediated via Y5 receptors.

AB - Central administration of neuropeptide Y (NPY) causes both anxiolysis and sedation. Previous studies suggest that both effects are mediated via NPY Y1 receptors. However, most of these studies were carried out before the advent of specific NPY receptor ligands. Therefore, a potential role for other NPY receptors in anxiety and sedation remains a possibility. In the present study, we addressed this issue by testing the effects of intracerebroventricular (i.c.v.) injection of NPY as well as specific receptor agonists for the Y1 receptor ([D-His(26)]NPY), Y2 receptor (C2-NPY), and Y5 receptor ([cPP(1-7),NPY(19-23),Ala(31),Aib(32),Gln(34)]hPP) in the elevated plus maze and open field tests. As with NPY, the Y1 agonist had a dose-dependent anxiolytic-like effect in both behavioral tests. In contrast to NPY, which caused significant sedation in the open field test, the Y1 agonist was without sedative effect. The Y2 agonist showed neither anxiolytic-like nor sedative effects. The Y5 agonist showed anxiolytic-like activity in both behavioral tests and caused sedation in the same dose range as NPY in the open field test. These results indicate that anxiolytic-like effects of i.c.v.-administered NPY in rats are mediated via both Y1 and Y5 receptors, whereas sedation is mediated via Y5 receptors.

KW - Analysis of Variance

KW - Animals

KW - Anxiety

KW - Behavior, Animal

KW - Dose-Response Relationship, Drug

KW - Exploratory Behavior

KW - Hypnotics and Sedatives

KW - Injections, Intraventricular

KW - Male

KW - Maze Learning

KW - Neuropeptide Y

KW - Peptide Fragments

KW - Rats

KW - Rats, Wistar

KW - Receptors, G-Protein-Coupled

KW - Receptors, Neuropeptide

KW - Receptors, Neuropeptide Y

KW - Time Factors

U2 - 10.1002/jnr.20200

DO - 10.1002/jnr.20200

M3 - Journal article

C2 - 15352219

VL - 77

SP - 723

EP - 729

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 5

ER -