Elevated anxiety-like behavior following ethanol exposure in mutant mice lacking neuropeptide Y (NPY)

BackgroundNeuropeptide 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+/+) 6 h after removal of a liquid diet containing 4.5% ethanol.MethodsNPY−/− 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 Six hours before elevated plus maze (EPM) testing, ED was replaced with CD in the ethanol-withdrawn group.ResultsEthanol-withdrawn NPY−/− mice showed significantly less open arm time and total proportion of time spent in the open arm of the EPM relative to ethanol-withdrawn NPY+/+ mice and when compared to NPY−/− and NPY+/+ mice that had access to the CD. On the other hand, ethanol-withdrawn NPY+/+ mice did not show altered EPM behavior relative to controls.ConclusionsCentral NPY is protective against anxiety-like behavior stemming from exposure to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.