Anxiolytic-Like Action of Neuropeptide Y: Mediation by Y1 Receptors in Amygdala, and Dissociation from Food Intake Effects

Abstract

from animal and human studies suggests that eropeptide Y (NPY) may be a potent endogenous .my tie. The anatomic structures mediating this action �fht peptide remain unknown. Furthermore, in addition �iIs anxiolytic-like effects, intracerebroventricular ""istration of NPY induces food intake through IIJpothalamic me chanisms, making the anxiolytic-like • of the peptide more difficult to interpret. The JI1JIOSi of this study was to examine the anatomic _rate for the effects of NPY on anxiety, and to _ferize the NPY receptors mediating these effects. lItrIctrebroventricular injection of NPY produced irrmse d food intake in free-feeding animals, and dose Itpmdent anticonflictlanxiolytic-like effects in an IIIbI ished animal model of anxiety, the Geller-Seifter Mlished by Elsevier Science Publishing Co., Inc.• Avenue of the Americas, New York, NY 10010 punished responding test. In contrast, microinjection of NPY into the central nucleus of the amygdala did not increase food intake in free-feeding animals, did not affect unpunished lever pressing for food, but did reproduce the anticonflictlanxiolytic-like effect with high potency. The selective NPY-YI agonist, p[Leu 31 ,Pro 3 4]NPY was approximately equipotent with native NPY in the conflict paradigm, and markedly more potent than the Y2 agonist, NPY 13 -3 6. Intrastriatal injections had no effect on conflict behavior. Thus, activation of YI receptors in the central nucleus of the amygdala produces effects similar to established anxiolytics without affecting food intake, suggesting that YI-receptors in the amygdala may be a substrate for anxiolytic actions of NPY.

The Effect of Intrahippocampal Injection of Group II and III Metobotropic Glutamate Receptor Agonists on Anxiety; the Role of Neuropeptide Y

“…NPY and mGluR ligands were given 20 min before the plus-maze test, whereas BIBO 3304 or BIIE 0246 was injected 10 min before those drugs. The doses and administration schedule were established in accordance with some earlier studies and our preliminary experiments (Shigemoto et al, 1997;Tatarczynska et al, 2001;Wierońska et al, 2005;Śmiałowska et al, 1996Heilig et al, 1993).…”

“…Moreover, neuropeptide Y (NPY) neurons and receptors took part in that effect (Wierońska et al, , 2005. NPY in the amygdala has been postulated to be a potent, endogenous anxiolytic (Heilig et al, 1993), as anxiolytic-like effects were observed after intraamygdalar NPY microinjection. Our previous results indicated that NPY neurons in the amygdala were regulated by Glu transmission, and that mGluRs were engaged in this regulation, as mGluR ligands changed the expression of NPY and/or NPYmRNA in that structure (Wierońska et al, , 2005.…”

Neuropeptide Y administration into the amygdala suppresses ethanol drinking in alcohol-preferring (P) rats following multiple deprivations

“…In spite of the mutual exclusivity of these pathways and the behaviors they mediate, it is intriguing that the sensitized effects of NPY during ethanol abstinence extend to multiple behaviors. More specifically, the orexigenic effects of NPY are mediated by the PVN (Stanley et al, 1985), the sedative effects by the posterior hypothalamic nucleus (Naveilhan et al, 2001), and the CeA mediates the suppressive effects of NPY on anxiety-like behavior (Heilig et al, 1993) and possibly ethanol drinking (Pandey et al, 2005); the effects of NPY on most, if not all, of these behaviors is augmented following periods of ethanol abstinence (Gilpin et al, 2005;Rimondini et al, 2005). Therefore, Voluntary consumption by P rats of amounts of ethanol similar to those in the present study produce pharmacologically significant blood ethanol levels, ranging from 50 to 200 mg% (Li et al, 1979;Murphy et al, 1986), and these levels of consumption by P rats produce tolerance to the effects of ethanol (Gatto et al, 1987; and perhaps even dependence (Kampov-Polevoy et al, 2000;Waller et al, 1982).…”

“…Because multiple amygdalar subcompartments (i.e. CeA and BLA) have been implicated in the anxiolytic effects of NPY (Heilig et al, 1993;Sajdyk et al, 1999Sajdyk et al, , 2008, it is not surprising that the amygdala is also implicated in the suppressive effects of the peptide on ethanol drinking. It is also logical that exogenously administered NPY more effectively suppresses ethanol drinking in abstinent relative to non-abstinent rats.…”

“…NPY decreases anxiety-like behavior in rats in multiple behavioral assays (Heilig et al, 1989;1992;Broqua et al, 1995;Britton et al, 1997;Sajdyk et al, 1999Sajdyk et al, , 2008. The anxiolytic effects of NPY appear to be mediated by the central nucleus of the amygdala (CeA; Heilig et al, 1993), although a role has also been suggested for the basolateral nucleus of the amygdala (Sajdyk et al, 1999(Sajdyk et al, , 2008. Since there is a body of evidence suggesting that the CeA is involved in the regulation of both Corresponding Author: Nancy E. Badia-Elder, Department of Psychology, IUPUI, 402 N. Blackford Street, LD 124, Indianapolis, IN 46202, Phone:317-278-1815, Fax:317-274-6756, Email: nbadiael@iupui.edu.…”