Assessment of ethanol consumption and water drinking by NPY Y(2) receptor knockout mice.
In recent years, pharmacological and genetic evidence have emerged suggesting that neuropeptide Y (NPY) and the NPY Y(1) receptor are involved with neurobiological responses to ethanol. Pharmacological data implicate a role for the NPY Y(2) receptor in ethanol self-administration. The purpose of the present study was to determine if genetic mutation of the Y(2) receptor would modulate ethanol consumption and/or ethanol-induced sedation. Here, we report that mutant mice lacking the NPY Y(2) receptor (Y(2)(-/-)), when maintained on a mixed 50% 129/ SvJ x 50 % Balb/cJ background, drink significantly less of solutions containing 3 or 6% (v/v) ethanol relative to wild-type (Y(2)(+/+)) mice. These mice drink normal amounts of solutions containing sucrose or quinine, have normal blood ethanol clearance, and show normal sensitivity to ethanol-induced sedation. However, Y(2)(-/-) mice that are backcrossed to a Balb/cJ background show normal consumption of ethanol, indicating that the contributions of the NPY Y(2) receptor to ethanol consumption are genetic background dependent. Consistent with previous data suggesting that NPY modulates water drinking, Y(2)(-/-) mice of both genetic backgrounds consume significantly more water than Y(2)(+/+) mice. The present results suggest roles for the NPY Y(2) receptor in the modulation of ethanol and water consumption.
Thiele
Todd E
TE
Department of Psychology and the Bowles Center for Alcohol Studies, University of North Carolina at Chapel Hill, Davie Hall, CB#3270, Chapel Hill, NC 27599-3270, USA. thiele@unc.edu
Naveilhan
Philippe
P
Ernfors
Patrik
P
D000428:Alcohol Drinking / Q000235:genetics; D000818:Animals; D004326:Drinking / Q000235:genetics / Q000502:physiology*; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology; D051379:Mice; D018345:Mice, Knockout; D011803:Quinine / Q000008:administration & dosage; D017476:Receptors, Neuropeptide Y / Q000235:genetics / Q000502:physiology*; D013395:Sucrose / Q000008:administration & dosage
D017476:Receptors, Neuropeptide Y; C095889:neuropeptide Y2 receptor; D000431:Ethanol; D013395:Sucrose; D011803:Quinine