Nociceptin/orphanin FQ is a 17-amino acid peptide classified as being a member of the opioid family, but binds with high affinity to the nociception receptor (NOP; also referred to as the opioid receptor-like 1 - ORL1) rather than mu, delta, or kappa opioid receptors (Meunier et al., 1995; Reinscheid et al., 1995). Dense expression of the peptide and its receptor within cortical and limbic regions suggest its role in emotional and motivational behaviors, particularly those related to stress, chronic alcohol exposure/withdrawal, and drinking. Increased expression of nociception and NOP mRNA in the CeA of rats selectively bred for high alcohol preference is suggested to relate to the high-anxiety and stress responsiveness in these animals (Ciccocioppo et al., 2007; Economidou et al., 2008). Pharmacological studies have demonstrated a role for the nociceptin/NOP system in regulation of alcohol self-administration, as well as withdrawal-related anxiety and drinking. For example, infusion of nociceptin into brain ventricles reduced alcohol conditioned reward as well as relapse-like behavior provoked by either stress or alcohol-related cues (Ciccocioppo et al., 2004; Martin-Fardon et al., 2000). Likewise, systemic administration of
