Central neuropeptide Y modulates binge-like ethanol drinking in C57BL/6J mice via Y1 and Y2 receptors.
Frequent binge drinking has been linked to heart disease, high blood pressure, type 2 diabetes, and the development of ethanol dependence. Thus, identifying pharmaceutical targets to treat binge drinking is of paramount importance. Here we employed a mouse model of binge-like ethanol drinking to study the role of neuropeptide Y (NPY). To this end, the present set of studies utilized pharmacological manipulation of NPY signaling, immunoreactivity (IR) mapping of NPY and NPY receptors, and electrophysiological recordings from slice preparations of the amygdala. The results indicated that central infusion of NPY, a NPY Y1 receptor (Y1R) agonist, and a Y2R antagonist significantly blunted binge-like ethanol drinking in C57BL/6J mice (that achieved blood ethanol levels >80 mg/dl in control conditions). Binge-like ethanol drinking reduced NPY and Y1R IR in the central nucleus of the amygdala (CeA), and 24 h of ethanol abstinence after a history of binge-like drinking promoted increases of Y1R and Y2R IR. Electrophysiological recordings of slice preparations from the CeA showed that binge-like ethanol drinking augmented the ability of NPY to inhibit GABAergic transmission. Thus, binge-like ethanol drinking in C57BL/6J mice promoted alterations of NPY signaling in the CeA, and administration of exogenous NPY compounds protected against binge-like drinking. The current data suggest that Y1R agonists and Y2R antagonists may be useful for curbing and/or preventing binge drinking, protecting vulnerable individuals from progressing to the point of ethanol dependence.
Department of Psychology, University of North Carolina, Chapel Hill, NC, USA.
Angela M
AM
Sparrow
Emily G
EG
Lowery-Gionta
Kristen E
KE
Pleil
Chia
C
Li
Gretchen M
GM
Sprow
Benjamin R
BR
Cox
Jennifer A
JA
Rinker
Ana M
AM
Jijon
José
J
Peňa
Montserrat
M
Navarro
Thomas L
TL
Kash
Todd E
TE
Thiele
D000428:Alcohol Drinking / Q000188:drug therapy* / Q000378:metabolism*; D000679:Amygdala / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000704:Analysis of Variance; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002492:Central Nervous System Depressants / Q000506:poisoning; D003216:Conditioning, Operant / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000506:poisoning; D005786:Gene Expression Regulation / Q000187:drug effects; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*
C092926:BIBP 3226; D002492:Central Nervous System Depressants; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; C062924:neuropeptide Y (13-36); C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; D000431:Ethanol; D001120:Arginine