JNJ-31020028 was shown to have high affinity for both human and rodent Y2 receptors. The antagonistic property of JNJ-31020028 for the Y2 receptor was demonstrated via inhibition of PYY-stimulated calcium response in KAN-Ts cells expressing a chimeric G protein. After subcutaneous administration, the Y2 antagonist was found to penetrate into the brain and dose dependently occupy Y2 receptor binding sites, demonstrating that the compound engaged its target in the CNS. JNJ-31020028 (15 mg/kg, s.c.) did reverse the anxiogenic effects of withdrawal from a single bolus dose of alcohol on the elevated plus-maze, confirming the anxiolytic-like properties of Neuropeptide Y2 antagonism. JNJ-31020028 has antidepressant like effects in the olfactory bulbectomized model.