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Updated: Jul 15, 2026

Elevated Plus Maze for Mice
Published on: December 22, 2008
Elevated anxiety-like behavior following ethanol exposure in mutant mice lacking neuropeptide Y (NPY)
Dennis R Sparta1, Jon R Fee, Darin J Knapp
1Department of Psychology, University of North Carolina, Chapel Hill, NC 27599-3270, USA.
Background:
Neuropeptide Y (NPY) is a neuromodulator with anxiolytic properties. Recent evidence suggests that NPY modulates neurobiological responses to ethanol. Because withdrawal from ethanol is associated with elevated anxiety-like behavior, and because central NPY modulates anxiety, we assessed anxiety-like behavior in mutant mice lacking normal production of NPY (NPY-/-) and in normal wild-type mice (NPY+/+) 6h after removal of a liquid diet containing 4.5% ethanol.
Methods:
NPY-/- and NPY+/+ mice on a pure 129/SvEv genetic background were given 6 days of access to a liquid ethanol diet (ED) or control diet (CD). Six hours before elevated plus maze (EPM) testing, ED was replaced with CD in the ethanol-withdrawn group.
Results:
Ethanol-withdrawn NPY-/- mice showed significantly less open arm time and total proportion of time spent in the open arm of the EPM relative to ethanol-withdrawn NPY+/+ mice and when compared to NPY-/- and NPY+/+ mice that had access to the CD. On the other hand, ethanol-withdrawn NPY+/+ mice did not show altered EPM behavior relative to controls.
Conclusions:
Central NPY is protective against anxiety-like behavior stemming from exposure to and/or withdrawal from ethanol. Targets aimed at NPY receptors may be useful compounds for treating anxiety associated with ethanol dependence.

