Past research on alcohol-dependent adults has shown that while the impetus to drink is often triggered by traumatic life events, it soon becomes a problem unto itself and has to be treated separately from whatever brought it on in the first place.
Scientists had long hypothesised that this is caused by physical changes in the brain, which create a kind of closed-loop that’s no longer responsive to any external stimuli, although identifying the exact mechanism behind these changes had remained elusive.
Now, a new study in the Journal of Neuroscience by researchers at the Texas A&M Health Science Centre College of Medicine finds that chronic alcohol consumption alters the function of individual neurons in the dorsomedial striatum, a part of the brain implicated in goal-driven behaviours.
Using an animal model, lead author Jun Wang, M.D., PhD., and a group of colleagues had discovered that alcohol changes the physical structure of medium spiny neurons, the main type of cell in the striatum. These neurons, which may be thought of as microscopic trees with many branches and tiny protrusions, or spines, each have either a D1 or a D2 dopamine receptor. The former stimulate action-oriented pathways in the brain, while the latter act as inhibitors.
The more alcohol an individual consumes, the more easily his/her D1 neurons become activated. “If these neurons are excited, you will want to drink alcohol,” Wang said. “You’ll have a craving.” This soon creates a cycle, where drinking causes easier activation, and activation leads to more drinking.
Wang’s team has found that this may be the result of an alcohol-exposed brain’s D1 neurons becoming more branched and growing more of the mature, mushroom-shaped spines – the ones that store long-term memories – than their abstaining counterparts.
While the total number of spines was the same in drinkers versus non-drinkers, the ratio of mature to immature ones was dramatically different. This has important implications for memory and learning in drug addiction. “When you drink alcohol, long-term memory is enhanced, in a way,” Wang said. “But this memory process is not useful – in fact, it underlies addiction since it affects the “go” neurons.”
As for the D2 neurons – no difference was observed in either the total number or the mature to immature ratio of spines, which suggests that alcohol addiction is driven by the “go” neurons alone.
To test their hypothesis, the researchers blocked the D1 neurons in a group of mice and supplied them with unlimited access to alcohol. In response, they showed a greatly-reduced desire to drink. Blocking the D2 neurons, however, had no effect.
“If we suppress this activity, we’re able to suppress alcohol consumption,” said Wang. “This is the major finding. Perhaps in the future, researchers can use these findings to develop a specific treatment targeting these neurons.”