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Peripheral and Central Administration of a Selective Neuropeptide Y Y1 Receptor Antagonist Suppresses Ethanol Intake by C57BL/6J Mice
Author(s) -
Sparta Dennis R.,
Fee Jon R.,
Hayes Dayna M.,
Knapp Darin J.,
MacNeil Douglas J.,
Thiele Todd E.
Publication year - 2004
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1097/01.alc.0000139829.67958.1a
Subject(s) - neuropeptide y receptor , ethanol , chemistry , antagonist , endocrinology , receptor , medicine , open field , neuropeptide , receptor antagonist , self administration , pharmacology , biochemistry
Background: Neuropeptide Y (NPY) is a 36–amino acid neuromodulator that is expressed throughout the central nervous system. Recent genetic and pharmacological evidence suggests that the NPY Y 1 receptor modulates ethanol intake. To further characterize the role of the Y 1 receptor, we examined voluntary ethanol consumption by mice after administration of [(−)‐2‐[1‐(3‐chloro‐5‐isopropyloxycarbonylaminophenyl)ethylamino]‐6‐[2‐(5‐ethyl‐4‐methyl‐1,3‐tiazol‐2‐yl)ethyl]‐4‐morpholinopyridine] (compound A), a novel and selective Y 1 receptor antagonist (Y1RA) that acts centrally on brain receptors when administered peripherally. Methods: C57BL/6J mice were habituated to drinking a 10% (v/v) ethanol solution by using a two‐bottle‐choice procedure and were then given an intraperitoneal (ip) injection (5 ml/kg) of the Y1RA (0, 25, 50, or 75 mg/kg). In a second study, mice were given intracerebroventricular infusion of the Y1RA (0, 30, or 100 μg). Finally, we determined whether the Y1RA alters open‐field locomotor activity, ethanol‐induced sedation (3.8 g/kg, ip), or blood ethanol levels. Results: Relative to control treatment, ip injection (50 and 75 mg/kg) and intracerebroventricular infusion (100 μg) of the Y1RA significantly reduced ethanol consumption and food intake without altering water drinking. However, the Y1RA did not alter open‐field locomotor activity, ethanol‐induced sedation, or blood ethanol levels. Conclusions: These data indicate that acute blockade of the NPY Y 1 receptor with a systemically bioavailable NPY Y1RA reduces voluntary ethanol consumption by C57BL/6J mice. These results are consistent with observations that hypothalamic infusion of NPY increases ethanol drinking by rats.