Neurobiological responses to ethanol in mutant mice lacking neuropeptide Yor the Y5 receptor

We have previously shown that voluntary ethanol consumption and resistance are inversely related to neuropeptide Y (NPY) levels in NPY-knockout (NPY - / -) and NPY-overexpressing mice. Here we report that NPY - / - mice on a m ixed C57BL/5J x 129/SvEv background showed increased sensitivity to locomot or activation caused by intraperitoneal (ip) injection of 1.5 g/kg of ethan ol, and were resistant to sedation caused by a 3.5-g/kg dose of ethanol. In contrast, NPY - / - mice on an inbred 129/SvEv background consumed the sam e amount of ethanol as wild-type (WT) controls at 3%, 6%, and 10% ethanol, but consumed significantly more of a 20% solution. They exhibited normal lo comotor activation following a 1.5-g/kg injection of ethanol, and displayed normal sedation in response to 2.5 and 3.0 g/ kg of ethanol, suggesting a genetic background effect. Y5 receptor knockout (Y5 - / -) mice on an inbre d 129/SvEv background showed normal ethanol-induced locomotor activity and normal voluntary ethanol consumption, but displayed increased sleep time ca used by 2.5 and 3.0 g/kg injection of ethanol. These data extend previous r esults by showing that NPY - / - mice of a mixed C57BL/6J x 129/SvEv backgr ound have increased sensitivity to the locomotor activation effect caused b y a low dose of ethanol, and that expression of ethanol-related phenotypes are dependent on the genetic background of NPY - / - mice. (C) 2001 Elsevie r Science Inc. All rights reserved.