Scientists investigating the role of dopamine in alcoholism have come up with some surprising evidence that may help to explain why addicts find it so difficult to stay away from booze. Publishing their findings in the Proceedings of the National Academy of Sciences, the researchers suggest that when an alcoholic stops drinking, the brain’s ability to use dopamine changes, altering the way that the reward system is wired.
Like many drugs, alcohol is known to stimulate the production of a chemical messenger called dopamine, which activates the so-called reward center of the brain. Previous studies into the nature of addiction have revealed that this dopamine response is significantly reduced in alcoholics, leading to a need to drink more in order to feel a buzz.
This reduction in dopamine levels causes what is known as a hypodopaminergic state, although little is known about what happens to the brain’s reward system when alcoholics try to stop drinking and enter a period of abstinence.
To investigate this, researchers began by examining brain tissue from deceased alcoholics. They found that these brains had fewer of a particular type of dopamine receptor than normal brains. Called D1 receptors, these are the sites on the membranes of neuronal cells to which dopamine binds, causing these neurons to become excited. Any reduction in these receptor sites would therefore be expected to decrease the brain’s responsiveness to dopamine, thereby explaining why alcohol fails to satisfy.
In addition, these brains were found to have fewer dopamine transporter sites, which allow for any unused dopamine to be sucked back up and recycled. So, as with D1 receptors, the disappearance of these sites is likely to hinder the brain’s ability to use dopamine.
The study's authors also note that the brains of deceased alcoholics displayed no reduction in D2 receptor sites, which bind with dopamine in order to inhibit, rather than excite, neurons. All in all, this evidence explains how alcohol dampens the brain’s reward center, compelling alcohol-dependent individuals to continually seek stimulation through booze.
Next, the study authors sought to determine the sequence of events leading to this situation. To do so, they used radiography techniques to track dopamine levels in the brains of alcohol-dependent rats that were denied alcohol for several weeks.
They discovered that dopamine levels dropped during the first six days, confirming the existing theory that acute alcohol withdrawal is characterized by a hypodopaminergic state. Interestingly, during this initial period, the availability of dopamine receptor sites and transporter sites were found to be normal.
However, after three weeks, the researchers noted that dopamine levels were in fact elevated, as the number of available receptor and transporter sites plummeted, so that the rats’ brains resembled those of the deceased alcoholic humans. This increase in extracellular dopamine levels is explained by the fact that less of it is able to bind to receptor sites, and therefore more of it remains unused in the gaps between neurons, known as synapses.
Significantly, at the three-week mark, the rats displayed continued behavioral effects associated with alcohol cravings.
As such, the study authors conclude that, while acute alcohol withdrawal may be associated with a hypodopaminergic state, prolonged abstinence actually leads to a hyperdopaminergic state – meaning dopamine levels in the brain are higher than normal. Crucially, they say that both of these states are representative of a dysfunctional reward system, and therefore increase a person’s vulnerability to relapse.