Pituitary adenylate cyclase-activating polypeptide (PACAP)-deficient mice display remarkable behavioral changes including increased novelty-seeking behavior and reduced hypothermia Induced by either serotonin (5-HT)(1A) receptor agonists or ethanol Because 5-HT1A receptors have been implicated in the development of alcohol dependence. we have examined ethanol preference in PACAP-deficient Mice using a two-bottle choice and a conditioned place preference test. as well as additive effects of ethanol and 50HT(1A) receptor agents on hypothermia PACAP-deficient mice showed an increased preference towards ethanol compared with wild-type mice However. they showed no preference for the ethanol compartment after conditioning an neither preference nor aversion to Sucrose or quinine The 5-HT1A ieceptor agonist 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) restored the attenuated hypothermic response to ethanol in the Mutants to similar levels in wild-type mice. with no effect in wild-types in contrast, the 5-HT1A receptor antagonist WAY-100635 attenuated the ethanol-induced hypothermia in wild-type mice. with no effect in the mutants. These results demonstrate increased ethanol preference in PACAP-deficient mice that may be mediated by 5-HT1A receptor-dependent attenuation of ethanol-induced central inhibition (C) 2009 Elsevier Inc All rights reserved