Neuropeptide Hypocretin’s Role in Addiction, Narcolepsy Studied

Hypocretin (neuropeptide) increase may be a factor in opiate craving and raising the number of hypocretin cells to near normal levels could reverse narcoleptic symptoms.

Chemical messenger hypocretin was found to be abundant in heroin users and lacking in people with narcolepsy.

Two discoveries -- one in the brains of people with heroin addiction and the other in the brains of sleepy mice -- shed light on chemical messengers in the brain that regulate sleep and addiction, UCLA researchers say.

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‘Hypocretin (neuropeptide) increase may be a factor in opiate craving and raising the number of hypocretin cells to near normal levels could reverse narcoleptic symptoms.’

In 2000, UCLA researchers discovered that human narcolepsy is caused by a loss of roughly 90 percent of the 80,000 brain cells containing hypocretin, also called orexin, a chemical messenger, or neurotransmitter, important in the regulation of sleep. Narcolepsy causes excessive sleepiness, sleep paralysis (a feeling of being conscious but unable to move), hallucinations and episodes of cataplexy, a partial or total loss of muscle control that is often triggered by a strong emotion such as laughter.

Narcolepsy affects about one in 2,000 to 3,000 people but can go undiagnosed for years, according to the National Sleep Foundation. The sleep disorder usually has its onset in childhood or adolescence.

In a new study, these researchers discovered that people addicted to heroin have, on average, 54 percent more hypocretin-producing neurons than do people without addiction. They confirmed, in mice, that opiates cause this increase. The increase in hypocretin cells lasted for as long as four weeks after discontinuation of the morphine treatment, well after morphine had left the animals' bodies.

Quiz on Narcolepsy
Narcolepsy is a chronic neurologic disorder that involves loss of brain's ability to regulate sleep and wake cycles normally. People having narcolepsy frequently sleep during the day as compared to those people who don't suffer from it. These sudden attacks of sleep can occur during any type of activity and at any time of the day. A normal sleep pattern involves the early stages of sleep then followed by deeper sleep stages and ultimately rapid eye movement (REM) sleep. In narcoleptic people, REM sleep occurs almost immediately in sleeping cycle and periodically during the waking hours.

Narcolepsy normally starts between ages of 15 and 25, but can become obvious at any age. In many cases, narcolepsy remains undiagnosed and hence untreated.

The researchers hypothesized that morphine, the active ingredient in heroin, might restore the missing hypocretin-producing neurons in people with narcolepsy. To test this idea, researchers used mice that were made narcoleptic by the loss of hypocretin cells and gave them morphine. The researchers found that morphine increased the number of hypocretin producing cells and their narcoleptic symptoms disappeared.

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The continued production of hypocretin in mice, after discontinuing morphine treatment, suggests that humans may continue producing hypocretin after they have stopped using heroin. However, further work in mice is necessary before this can be recommended as a treatment for narcolepsy in people. Next, researchers would like to find out if reducing "excess" hypocretin cells -- or blocking the action of the hypocretin peptide that they release -- could make long-term withdrawal from opiates easier and prevent relapse.

Source-Eurekalert

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