Researchers have discovered that the brains of heroin addicts harbor a greater number of neurons that produce hypocretin, a molecule involved in arousal and wakefulness, and one lacking in abundance in people with narcolepsy. In mice with narcolepsy, these researchers went on to show, administering morphine - an opioid similar to heroin - reversed the symptom of cataplexy (loss of muscle tone), suggesting that altering hypocretin levels could potentially serve as a therapeutic strategy for treating narcolepsy. Narcolepsy is a condition affecting approximately 200,000 people in the U.S., and is characterized by excessive daytime sleepiness and cataplexy. Although scientists have developed treatments to address sleepiness and cataplexy, they do not restore normal function and can have unpleasant side effects. In previous studies, Thomas Thannickal and other researchers had found that narcolepsy was linked to a loss of hypocretin-producing neurons in the brain. Interestingly, they also noticed that the brain of a heroin addict enrolled in the study harbored more neurons producing hypocretin compared to other brains. Here, Thannickal and colleagues built on their previous work and investigated whether an abundance of hypocretin-producing neurons was characteristic of other opiate addicts. They studied postmortem brain tissue from four heroin addicts and found their brains exhibited an average 54% increase in hypocretin neurons compared to controls. Long-term administration of morphine to mice resulted in a similar increase in hypocretin neurons, an effect that persisted several weeks after morphine administration was halted. Turning back to narcolepsy, the authors found that administering morphine to narcoleptic mice deficient in hypocretin neurons restored hypocretin cell numbers and ameliorated cataplexy symptoms. Thannickal et al. say that future human trials should determine whether opiates or better yet, novel opiate-like compounds, could be used to restore hypocretin levels and treat narcoleptic patients. They also say that future research should investigate whether decreasing hypocretin levels could combat opiate addiction in humans.
Science Translational Medicine