Oxytocin Deficit in Heavy Alcohol Drinkers

项目总结

Project Summary Alcohol use disorder (AUD) is a major public health concern in the US and worldwide with extremely limited number of FDA approved medications that are not effective in everyone. Recently the neuropeptide, oxytocin, was proposed as a potential treatment for alcohol use disorder, but the neuronal mechanism underlying its therapeutic potential is elusive. Elucidating chronic effects of alcohol on levels of oxytocin in the central nervous system is essential to help understand its therapeutic mechanism and eventually identify patients that would receive the greatest benefit from the treatment. However, acquiring direct measures of oxytocin in the central nervous system of humans is complex or impossible, and frequently brain levels of oxytocin are assumed based on known blood concentrations. Nevertheless, a relation between the central and blood levels of oxytocin is unclear and animal studies are needed to reveal chronic effects of alcohol on levels of oxytocin in the central nervous system and to explore the relation between the central and blood levels of oxytocin. Nonhuman primates provide an exceptionally beneficial translational model for human alcohol use disorder due to their genetic, anatomical, and physiological similarities to humans, and because they exhibit wide individual differences in the amount of alcohol they voluntarily drink. In this project we propose to measure levels of endogenous oxytocin in the pituitary tissue, cerebral spinal fluid and blood samples collected from monkeys that underwent a standard alcohol self-administration protocol for 12 months. First, we will test if levels of oxytocin in the pituitary and CSF decrease with an increase in alcohol intake (Aim 1). Then we will test whether levels of oxytocin in the pituitary and CSF correspond to blood concentration of oxytocin in primates (Aim 2). Thus, this project will provide important evidence on oxytocin levels across heavy drinking individuals and would significantly aid in the approach toward personalized use of the potential oxytocin therapy for alcohol use disorder.