“I’ll just come out for one drink.” Oh how we repeatedly kid ourselves. It’s good to see that many of us have faith that we can call upon willpower to turn down the offer of just one more, but often it seems we should resign ourselves to the fact that it rarely is just the one cheeky beverage. But what drives alcohol-seeking behavior? Scientists seem to be slowly unraveling this story.
According to new research, alcohol changes both the structure and function of a specific population of cells in a region of the brain that is known to drive goal-directed behaviors. Ultimately, the alterations made these cells more excitable, sending signals that create an urge for more booze.
The discovery, made by researchers at Texas A&M University, follows on from earlier work by the same group that found alcohol facilitates an important neuronal process in cells located in an area of the brain called the dorsomedial striatum (DMS). This process, called synaptic plasticity, involves alterations to the strength of the junctions between neurons – the synapses – across which information flows.
To delve a little deeper, the team engineered mice so that the cells which make up the majority of the DMS, called medium spiny neurons, were fluorescent. These spindly, spider-like neurons possess many branching structures that are complete with tiny protrusions called spines that serve as an input point. They are also adorned with one of two types of receptor for our brain’s “pleasure” chemical, dopamine, and so can be referred to as either D1 or D2 neurons. The former are involved in a “Go” pathway which encourages action, whereas the latter do the opposite and drive “No-Go” behaviors.
While dopamine is known to be involved in drug reinforcement, providing the rewarding effects of commonly abused drugs, its role in addiction has been less clear. That being said, the results from this current study, published in the Journal of Neuroscience, seem to implicate the D1 receptor in addiction. By repeatedly exposing mice to alcohol, either through systemic administration or consumption, the researchers found that D1 neurons became more excitable, requiring less stimulation to fire.
“If these neurons are excited, you will want to drink alcohol,” lead author Jun Wang said in a statement. “You’ll have a craving.”
So when the D1 neurons become activated, they drive “Go” behaviors, which in this case is an action that will increase alcohol intake. But this leads to a vicious cycle: more booze further decreases the activation threshold, which in turn drives more drinking behavior.
The researchers think this could be related to the structural changes in the spiny neurons that alcohol seems to trigger. Compared with controls, mice on the booze had longer branches and more mature, "mushroom-shaped" spines on their D1 neurons, which are important for long-term memory. Interestingly, though, the number of spines did not differ between the two groups. But when they looked at D2 neurons, the same differences in spine maturity were not observed.
Because such alterations in spine morphology play a significant role in synaptic plasticity and have been linked to the process of learning and memory, the researchers think that these booze-driven adaptations may drive the development of alcoholism. While this may be a common yet poorly understood disorder, these findings could open up new avenues for research into potential treatments. And that may not be so out of reach, because the team found that partially blocking the D1 receptor with a drug actually suppressed alcohol consumption in the mice, but not when D2 was inhibited.
“My ultimate goal is to understand how the addicted brain works,” said Wang, “and once we do, one day, we’ll be able to suppress the craving for another round of drinks and ultimately, stop the cycle of alcoholism.”
