For the first time, researchers show that depriving rats of sleep causes a brain region associated with reward-seeking addictive behavior to produce much higher levels of an opioid substance that drives eating for pleasure, not for hunger.
“These systems are important in addiction and other psychiatric disorders where there is a disregulation of motivated behavior,’’ explains lead author Dr. Brian Baldo, assistant professor of psychiatry. This may be why you’re driven to eat carbohydrates and fats when you’re sleep-deprived – your opioid system is telling you to pick up the spoon.”
The paper, published in the journal Neuropsychopharmacology, is a collaboration between Baldo, whose laboratory studies the neural basis of eating disorders and addiction, and Dr. Ruth Benca, a sleep researcher.
“We’ve long known that when you deprive rats of sleep, one of the first things they do is increase their food consumption and their preference for higher-reward food,’’ says Benca, professor of psychiatry and research director of the Wisconsin Sleep Center.
Benca says her human patients who have various sleep disorders that cause sleep loss may gain weight, a phenomenon also experienced by people such as medical residents who work long hours that disrupt a regular sleep cycle.
And a recent Colorado study showed that sleep-deprived people don’t eat more at meals but instead increase their eating of snacks, particularly in the evening when they are most sleep-deprived.
To study the phenomenon, the Wisconsin researchers deprived rats of sleep by having them walk on a treadmill when sleepy. To make sure the results reflected sleep deprivation, they compared them to rats that had the same amount of exercise (but during waking), and hungry rats on a reduced diet.
The brain scans were striking: only the sleep-deprived rats showed a strong response in the striatal complex, a brain region that includes the nucleus accumbens. The nucleus accumbens regulates the effects of both natural rewards and drugs of abuse.
Throughout the nucleus accumbens and striatum, sleep loss increased activity in the gene that produces an opioid peptide called proenkephalin. This is a naturally occurring, small protein molecule that activates the same brain receptors as drugs like morphine or heroin.
“This is a system that produces ‘liking’ and craving,’’ Baldo says, explaining that the opioids tend to magnify the pleasures of eating junk food, including sweet or high-fat foods. “Normally, this gene tells the animal to keep eating pleasant-tasting foods, beyond any metabolic or nutritional need; after eating, the opioid produced by the gene goes down. But when the animals experienced sleep loss, the gene appeared to get stuck in the ‘on’ position.”
Sleep deprivation also produced more of another opioid protein called prodynorphin. This chemical is associated with an irritable or depressed mood, and is often high in the brains of people who commit suicide or experience drug withdrawal.
In addition to being the first proof that a brain system that drives sweet or high-fat food “snacking” is overactive in the sleep- deprived, Baldo says the study highlights some potential targets for drugs that could cure the food cravings. And Benca says it underlines an important behavioral lesson: “If you want to lose weight, it helps to get enough sleep.”
The research was supported by grant RO1 HL086465 from the National Heart, Lung and Blood Institute and grant RO1 MH074723 from the National Institute of Mental Health. Benca reported previous work as a consultant for Merck and Sanofi-Aventis as a possible conflict of interest. Read the paper
University of Wisconsin School of Medicine and Public Health