The δ2-opioid receptor antagonist naltriben reduces motivated responding for ethanol

Rationale: Given that alcoholics drink for different reasons, it is not likely that a single pharmacotherapeutic agent will be equally effective for: all alcoholics. Hence, the development of new pharmacotherapeutic agents that are capable of reducing alcohol intake remains an important focus in the field of alcohol research. Objective: The objective of the present study was to examine the effects of the delta(2) receptor antagonist naltriben (0.60-4.0 mg/kg) on operant responding maintained by the presentation of ethanol (EtOH) or saccharin in alcohol-preferring (P) rats. Methods: P rats were trained under a concurrent schedule [fixed ratio (FR)4-FR4] to press one lever for EtOH (10% v/v) and another for saccharin (0.0125-0.05% w/v) during a 60-min session. Naloxone, a non-specific opioid receptor antagonist, served as a reference antagonist. Results: When responding maintained by EtOH and saccharin were equated under baseline conditions, naloxone (0.003125-0.75 mg/kg) reduced levels of EtOH-maintained responding by 46-82%. None of the naloxone doses significantly reduced responding maintained by saccharin. Naltriben (0.9-4.0 mg/kg) reduced EtOH-maintained responding by 44-76%, while saccharin-maintained responding was reduced only by the highest dose of naltriben (4.0 mg/kg). Analysis of the EtOH within-session response pattern revealed that naloxone suppressed EtOH-maintained responding during the entire operant session and led to early termination of responding. Low doses of naltriben (0.90 mg/kg and 1.2 mg/kg) suppressed responding during the latter portion of the operant session, while higher doses (2.0, 3.0, 4.0 mg/kg) decreased responding during the entire sessionand led to early termination of responding. Conclusions: The results of the present study strengthen previous reports from our laboratory suggesting that naltriben, the selective delta(2) opioid receptor antagonist, suppresses EtOH self-administration in rats selectively bred for high EtOH consumption. The results also suggest that naltriben may be a potential candidate for use as a pharmacotherapeutic agent in the treatment of EtOH dependence.