Neurobiological responses to ethanol in mutant mice lacking neuropeptide Y or 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 mixed C57BL/6Jx129/SvEv background showed increased sensitivity to locomotor activation caused by intraperitoneal (ip) injection of 1.5 g/kg of ethanol, 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 same 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 locomotor 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 inbred 129/SvEv background showed normal ethanol-induced locomotor activity and normal voluntary ethanol consumption, but displayed increased sleep time caused by 2.5 and 3.0 g/kg injection of ethanol. These data extend previous results by showing that NPY -/- mice of a mixed C57BL/6Jx129/SvEv background have increased sensitivity to the locomotor activation effect caused by a low dose of ethanol, and that expression of ethanol-related phenotypes are dependent on the genetic background of NPY -/- mice.
Thiele
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TE
Department of Psychology, University of Washington, Box 351525, Seattle, WA 98195, USA. thiele@u.washington.edu
Miura
G I
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Marsh
D J
DJ
Bernstein
I L
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Palmiter
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RD
D000428:Alcohol Drinking / Q000235:genetics*; D000818:Animals; D002492:Central Nervous System Depressants / Q000097:blood / Q000494:pharmacology*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009043:Motor Activity / Q000187:drug effects* / Q000235:genetics; D009478:Neuropeptide Y / Q000235:genetics*; D017476:Receptors, Neuropeptide Y / Q000235:genetics*
D002492:Central Nervous System Depressants; D009478:Neuropeptide Y; D017476:Receptors, Neuropeptide Y; C100568:neuropeptide Y5 receptor; D000431:Ethanol