Endogenous Nociceptin (Orphanin FQ) Suppresses Basal Hedonic State and Acute Reward Responses to Methamphetamine and Ethanol, but Facilitates Chronic Responses

摘要: The opioid peptide nociceptin (orphanin FQ) suppresses drug reward, self-administration, and impedes some of the processes believed to underlie transition addiction. As virtually all previous studies have used administration receptor agonists evaluate role on addiction-like behavior, current study a pharmacological (nociceptin antagonist) genetic knockout mice) approach elucidate endogenous nociceptin. antagonist UFP-101 induced modest place preference, enhanced conditioned preference by methamphetamine. In agreement with this, mice had slightly methamphetamine ethanol preferences compared wild-type mice. This effect did not appear depend differences in learning ability, as weaker-conditioned aversions lithium chloride, κ-opioid agonist, U50488H, general opiate antagonist, naloxone. development behavioral sensitization was lower mice, attenuated Additionally, consumption two-bottle choice test though ethanol-stimulated locomotion stronger. Whereas rewarding following chronic treatment, measured conditioning, strengthened this absent These results suggest that N/OFQ basal drug-stimulated increases hedonic state, plays either permissive or facilitatory