Within-subject comparison of the psychopharmacological profiles of oral oxycodone and oral morphine in non-drug-abusing volunteers

RATIONALE: The opioid peptide beta-endorphin (beta-E) is synthesized by the pro-opiomelanocortin gene in response to environmental stressors and alcohol administration and is implicated in the behavioral sequelae associated with these stimuli. OBJECTIVES: We sought to determine the influence of beta-E on the stress response by evaluating basal measures of anxiety as well as on EtOH-induced anxiolytic behavior using transgenic mice that differ with respect to beta-E. METHODS: Anxious behavior was evaluated for male and female heterozygous, wild-type, and beta-E knockout mice using the Light-Dark Box and Plus Maze assays. Subsequent tests evaluated behavior 20 min after administration of intraperitoneal saline or EtOH (0.5, 1.0, and 1.5 g/kg). RESULTS: We observed a direct relationship between beta-E levels and the percentage of entries into open arms of the Plus Maze as well as the time spent in either the open arms or the light compartment of the Light-Dark box during basal conditions, suggesting that this peptide normally inhibits anxious behavior. However, mice lacking beta-E demonstrated an exaggerated anxiolytic response to EtOH in these assays. CONCLUSIONS: These data suggest that beta-E moderates the response to stressful stimuli and supports the hypothesis that this peptide influences the behavioral effects of EtOH.