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

Abstract

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.

Silver nanoparticle exposure induces rat motor dysfunction through decrease in expression of calcium channel protein in cerebellum

“…Consistent with the result from the literature on Mn (Oszlanczi et al, 2010), our data suggested that chronic treatment with AgNPs exerted an increase in the resting time as well as a decrease in the moving distance and moving velocity, revealing the depletion of horizontal activity in the rats. The difference of the rearing frequency between AgNPs-treated rats and the controls demonstrated that AgNPs exerted an inhibitory effect on the vertical exploratory behavior of animals, which was in line with preceding reports on the rats with sedation treatment (Sorensen et al, 2004). Some other indexes such as the number of entries into the center showed the similar down-regulating trend upon AgNPs exposure, indicating AgNPs were able to cause impairment of spontaneous behavior in rats.…”

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

“…Although we did not demonstrate causality, only association of NPY with behavioral effects, multiple studies have already determined anxiolytic effects of NPY (for a review, see Heilig, 2004). Increased NPY expression or NPY administration is associated with anxiolytic effects, whereas decreased NPY expression or blockade of its receptors is anxiogenic (Bannon et al, 2000;Heilig and Murison, 1987;Sajdyk et al, 1999;Sorensen et al, 2004;Tschenett et al, 2003). Accordingly, increased NPY expression in the hippocampus after prenatal betamethasone exposure is congruent with anti-anxiety effects.…”

Effects of NPY and the specific Y1 receptor agonist [d-His26]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats

“…The effect of [D-His 26 ]-NPY on nicotine withdrawal was investigated as this compound, in contrast to NPY, has a low affinity for the Y5 receptor (NPY, Ki of 0.28 nM for Y1, Ki of 1.5 nM for Y5; ]-NPY, Ki of 2.0 nM for Y1, Ki of 34.6 nM for Y5) (Mullins et al, 2001). Activation of the Y5 receptor has been suggested to mediate NPY's sedative effects while NPY's anxiolytic and antidepressant-like effects have been suggested to be mediated via the activation of the Y1 receptor (Ishida et al, 2007;Redrobe et al, 2002a;Sorensen et al, 2004). Experiment 1 and 2 indicated that NPY and [D-His 26 ]-NPY elevated the brain reward thresholds of the saline-treated control rats.…”