Abstract

The mechanism by which the opioid antagonist naltrexone suppresses overconsumption of ethanol is unclear. Oral ethanol consumption in humans increases hypothalamic-pituitary-adrenal (HPA) activity, and recent studies suggest that naltrexone may reduce ethanol consumption by modifying the HPA-stimulating effects of ethanol. The purpose of this study was to measure in rhesus monkeys the effects of ethanol and naltrexone, alone and in combination, on plasma levels of adrenocorticotropin hormone (ACTH). Nine adult male and female rhesus monkeys with chronic, indwelling intravenous catheters were maintained on tethers that allowed ethanol delivery and blood sampling. In one study, the monkeys received intramuscular injections of saline or 0.32 mg/kg naltrexone followed by noncontingent intravenous bolus infusions of saline or 0.3 to 1.8 g/kg ethanol. In a second study, other monkeys were given intramuscular injections of saline or 0.01 to 0.3 mg/kg naltrexone and subsequently responded on levers to receive intravenous saline or ethanol 0.03 g/kg per injection. Ethanol, delivered either response contingently or noncontingently, did not produce systematic changes in ACTH plasma levels. Naltrexone alone produced increases in plasma ACTH that were attenuated by the subsequent administration of noncontingent or response-contingent ethanol. Naltrexone also produced dose-dependent reductions in intravenous ethanol self-administration. Linear regression analysis indicated that ethanol intake was negatively correlated with the plasma levels of ACTH over time. The route of administration may modulate ethanol's effects on HPA activity. Ethanol may attenuate naltrexone's effect on the HPA axis by impairing HPA axis sensitivity to other stimuli. The negative correlation between ethanol intake and ACTH levels supports the notion that naltrexone's effect of increasing HPA axis activity may be related to its ability to suppress ethanol consumption.

Talk to us

Join us for a 30 min session where you can share your feedback and ask us any queries you have

Schedule a call

Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.