Dip in dopamine linked with drug addiction

 17 March 2017   Research News

By Deborah Oakley

Regular use over many years of drugs in a class known as stimulants, including cocaine, is associated with lower levels of the brain chemical dopamine, which plays a key role in how the brain processes reward, motivation and pleasure. This may explain why these drugs are highly addictive, and suggests that targeting dopamine could help to treat addiction, according to a review of current research published this week in JAMA Psychiatry.

The review was led by Oliver Howes, of the MRC London Institute of Medical Sciences (LMS), and involved examining the action of dopamine through detailed analysis of 31 studies involving brain scans of long-term users of the drugs cocaine, amphetamine, and its close cousin methamphetamine.

Many of these studies used only small groups of people because scanning the brains of drug users is a difficult and sometimes expensive process. By drawing together the results of many such studies, this review draws a clear link between amphetamine, cocaine and methamphetamine use and blunted dopamine levels.

Up to 53 million people globally used amphetamine in 2015, whilst up to 20 million used cocaine, according to the World Drug Report*. Addiction to these drugs is common, but there is no effective treatment, say the researchers.

“One of the reasons for the failure to develop effective treatments might be our lack of understanding about the exact nature of the chemical changes in the brains of long-term users,” says Howes. “There is an urgent need to develop new, and more effective treatments.”

The brains of healthy people (left) have higher levels of a molecule that transports dopamine (orange, red) than those who use methamphetamine (right). (Image courtesy: Prof Nora Volkow, National Institute on Drug Abuse, Bethesda, Maryland)

It has been known that when an individual first uses one of these drugs, it raises dopamine levels in their brain and this produces a euphoric feeling, or “high”. This review suggests that after repeated drug use the brain may compensate, by dampening down baseline levels of dopamine. This abnormal brain state may induce a negative feeling, and create the cravings that may drive addiction, says Abhishekh Ashok, also of the LMS, who played a key role in the review.

“If we can develop treatments to restore normal dopamine levels, we may one day be able to treat addiction,” says Ashok. “We may also be able to predict how likely it is that a given person will respond to this treatment by measuring the numbers of dopamine receptors in an individual’s brain.”

These findings add to the conclusions of another review on drugs and dopamine by the same team, published in Nature last November. The study showed that regular, long-term cannabis use blunts levels of dopamine in the brain. Read more here.

The LMS scientists worked with researchers at King’s College London and the National Institute of Drug Abuse, USA.

* World Drug Report 2015, United Nations Office on Drugs and Crime

Delving deeper into dopamine

Also this week, Howes and team published a review in Molecular Psychiatry about the role that dopamine plays in bipolar disorder.

People with bipolar experience severe mood changes, moving between the lows of severe depression and the highs of mania. According to the researchers, treatments that target dopamine are becoming increasingly popular, but it has not been known exactly how changes in dopamine can alter mood.

In this review, the LMS team shows that when an individual experiences mania, they have higher than normal levels of dopamine receptors in a part of their brain called the striatum, which is involved with reward. This allows cells in the striatum to absorb extra dopamine and makes the brain’s reward system hyper responsive, leading to racing thoughts and impulsive behaviour.

The researchers also show that dopamine levels dip during the depressive phase of bipolar by a second, separate mechanism. This happens because there is an increase in the amount of dopamine transporter molecules, which are known to move dopamine into storage compartments inside cells, where it cannot be used.

Together, these findings suggest that bipolar may be caused by an inability to keep dopamine levels within a normal and healthy range. “If we can better understand the brain biology that underpins this disorder, we may be able to improve the use of current treatments and develop more effective alternatives,” says Ashok.