Scientists have discovered that the desire to drink alcohol varies with time of day and is strongest during the hours of dark. Using mice, they also showed that a drug that targets an immune receptor in the brain reduces the impulse to drink alcohol, especially in the evening.

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A new study has shown that a certain drug may be able to switch off people's desire to drink alcohol during the evening.

The researchers, from the University of Adelaide in Australia, report their work in the journal Brain, Behavior, and Immunity.

They believe that their study is among the first to show that the brain's immune system is linked to desire for night-time alcohol consumption, and they hope that it will improve scientific understanding of what drives drinking behavior.

Alcohol consumption is a global public health issue that accounts for around 5 percent of the "global burden of disease and injury."

Worldwide, 3.3 million people die every year (5.9 percent of all deaths) because of their harmful use of alcohol. Around 25 percent of deaths among people aged 20 to 39 years are attributed to alcohol.

In the United States - where it is thought that around 88,000 people die every year from alcohol-related causes - alcohol use is the third leading preventable cause of death, with the first being tobacco use and the second being lack of exercise and poor diet.

In a 2010 resolution, the World Health Assembly urged all countries to strengthen their responses to "public health problems caused by the harmful use of alcohol."

Understanding the biology of alcohol use

As lead study author Jon Jacobsen, a Ph.D. student in the University of Adelaide's Discipline of Pharmacology, explains, "Alcohol is the world's most commonly consumed drug, and there is a greater need than ever to understand the biological mechanisms that drive our need to drink alcohol."

Previous research has shown that circadian rhythm - that is, the mental, physical, and behavioral changes that follow a roughly 24-hour cycle - influences drug-induced reward signals in the brain and that the peak time for these signals is during the evening.

Circadian rhythm also has an effect on immune responses, and research in rodents shows that these also peak at night-time, when they are active.

Scientists are also beginning to appreciate that the immune system is involved in drug-induced reward. However, while it seems that an immune receptor in the brain called Toll-like receptor 4 (TLR4) plays a key role, it is not clear how its influence relates to circadian rhythm.

"Our body's circadian rhythms affect the 'reward' signals we receive in the brain from drug-related behavior, and the peak time for this reward typically occurs during the evening, or dark phase," Jacobsen explains.

"We wanted to test what the role of the brain's immune system might have on that reward, and whether or not we could switch it off."

The role of the brain's immune system

The researchers decided to test their ideas by giving mice (+)-Naltrexone, which is a drug that blocks TLR4. The drug is known to reverse neuropathic pain and reduce "opioid and cocaine reward and reinforcement."

They found that the mice's motivation to consume alcohol varied with time of day and was greatest at night-time. This circadian pattern was also evident in genes that influence reward and TLR4, note the authors.

When the team tested the effect of (+)-Naltrexone on the mice, it was found that it reduced TLR4 gene expression and that the effect was strongest "during the dark cycle."

They also found that the mice showed less reward-like behavior when given (+)-Naltrexone, and that this effect was also "most pronounced during the dark cycle."

Jacobsen says that they "concluded that blocking a specific part of the brain's immune system did in fact substantially decrease the motivation of mice to drink alcohol in the evening."

Senior study author Prof. Mark Hutchinson - of the neuroimmunopharmacology laboratory that conducted the study - says that the work forms part of an emerging field that "highlights the importance of the brain's immune system in the desire to drink alcohol."

He and his co-authors suggest that further studies should now be done to find out whether or not these discoveries are also true of humans.

"Given the drinking culture that exists in many nations around the world, including Australia, with associated addiction to alcohol and related health and societal issues, we hope our findings will lead to further studies," adds Prof. Hutchinson.

"Our studies showed a significant reduction in alcohol drinking behavior by mice that had been given (+)-Naltrexone, specifically at night-time when the reward for drug-related behavior is usually at its greatest."

Jon Jacobsen