New Delhi: New research in mice suggests activity in the BNST may be linked to compulsive alcohol-seeking after a period of abstinence, potentially offering a future way to identify people at higher risk of relapse.
Periods of abstinence from alcohol are generally associated with important health benefits, but researchers are investigating why some people with alcohol use disorder experience a powerful return to drinking after stopping.
A new study involving mice has identified changes in activity in a small brain region called the bed nucleus of the stria terminalis (BNST) that appear to occur before compulsive alcohol-seeking behaviour. The findings could eventually contribute to new approaches for identifying people who may be particularly vulnerable to relapse.
The research does not show that abstinence itself causes alcohol use disorder or that everyone who stops drinking will subsequently experience stronger cravings. Instead, it highlights a possible biological mechanism that may contribute to relapse in a subset of individuals.
Study examines behaviour after alcohol abstinence
Researchers first gave mice long-term voluntary access to alcohol. The animals were then subjected to a period during which alcohol was no longer available.
After this forced abstinence period, the researchers examined how the animals behaved when alcohol was made available again.
A subset of the mice displayed what researchers described as aversion-resistant alcohol intake. In other words, they continued drinking even when quinine was added to the alcohol, making it increasingly bitter and unpleasant.
These mice subsequently consumed greater quantities of the highly bitter alcohol than mice that had not undergone the same abstinence period.
The observation suggests that, in some circumstances, changes associated with abstinence may contribute to behaviour resembling compulsive drinking.
Researchers focus on the BNST
The team then investigated activity in the BNST, a small structure located deep within the brain.
The region has previously been associated with processes relevant to alcohol use disorder, including stress, anxiety and negative emotional states.
Researchers monitored activity in a particular population of cells within the BNST while the abstinent mice were exposed to situations associated with previous alcohol availability.
The results provided an important clue.
When abstinent mice were returned to an environment where alcohol had previously been available, they sometimes attempted to drink even when the drinking spout contained only water.
These alcohol-seeking attempts were accompanied by activity in the BNST.
Stronger BNST activity seen in some mice
The researchers found a notable difference between the animals.
Abstinent mice that subsequently developed a preference for very bitter alcohol showed more than twice the BNST activity compared with mice that did not develop the same behaviour.
This suggests that increased activity in this brain region may be associated with the development of particularly persistent alcohol-seeking behaviour after abstinence.
However, the finding comes from an animal study and should not be interpreted as evidence that BNST activity can currently predict relapse in humans.
Further research will be needed to establish whether similar changes occur in people with alcohol use disorder.
Brain activity appeared before alcohol was available
One of the more significant observations came when researchers examined the timing of the BNST activity.
The researchers detected changes in BNST activity before the abstinent mice were given access to the bitter alcohol.
This raises the possibility that activity in the region may reflect a state of heightened vulnerability rather than simply being a response to consuming alcohol.
If similar patterns are eventually demonstrated in humans, researchers could investigate whether brain activity associated with alcohol-related cues might help identify people at greater risk of relapse.
Such an approach remains experimental and would require substantial validation before it could become a clinical screening method.
Why relapse remains difficult to predict
Alcohol use disorder is a complex condition influenced by biological, psychological and social factors.
Although clinicians have established methods for diagnosing the disorder and several treatments are available, predicting exactly who will relapse remains difficult.
People can experience cravings and alcohol-seeking behaviour for different reasons, including exposure to environmental cues, stress, emotional difficulties and changes in brain reward and stress systems.
The new research adds another potential biological component to this picture.
Rather than viewing relapse only as a matter of willpower or environmental exposure, researchers are examining how specific neural circuits may influence the ability to resist alcohol despite negative consequences.
What is the BNST?
The bed nucleus of the stria terminalis is a group of structures located in the forebrain.
It is involved in several processes associated with stress and emotional responses.
Researchers studying addiction have become increasingly interested in the BNST because of its connections with brain systems involved in motivation, stress and negative emotional states.
The region is particularly relevant to research examining anxiety-like behaviour and the effects of prolonged exposure to addictive substances.
The new findings suggest that specific populations of BNST cells could also contribute to alcohol-seeking after abstinence.
Findings do not mean abstinence is harmful
The researchers emphasise a distinction that is important when interpreting the findings.
Abstinence from alcohol has well-established health benefits, and stopping harmful alcohol consumption remains an important part of treatment for many people with alcohol use disorder.
The mouse study does not suggest that people should continue drinking to avoid relapse.
Instead, it raises a different question: Why do some individuals remain vulnerable to compulsive drinking after they have stopped?
Understanding that vulnerability could help researchers develop more personalised strategies for preventing relapse.
Alcohol use disorder remains a major health concern
Alcohol-related harm remains a significant public health issue.
Alcohol use can affect the liver, heart, brain and other organs and is associated with a range of chronic diseases and injuries.
Alcohol use disorder can also affect relationships, employment, mental wellbeing and overall quality of life.
Despite the availability of treatment, many people who could benefit from professional support do not receive it.
The researchers argue that better ways of identifying people at higher risk could potentially improve treatment strategies and help clinicians intervene before a relapse occurs.
What the study does not yet explain
Although the BNST findings are promising, several questions remain unanswered.
Scientists do not yet know exactly why BNST activity increases following abstinence or which individual groups of cells are responsible for the observed pattern.
It is also unclear whether the changes observed in mice correspond directly to the neural activity seen in humans with alcohol use disorder.
Another important question is whether manipulating BNST activity could actually reduce compulsive alcohol-seeking.
Answering these questions will require additional laboratory research and human studies.
Human research could provide the next clue
The research team is now interested in determining whether similar BNST activity can be observed in people with alcohol use disorder during early abstinence.
Human research could help establish whether the brain region plays a comparable role in alcohol cravings and relapse.
If similar patterns are found, researchers could eventually investigate whether BNST activity has value as a biomarker.
However, a potential screening tool would need to be tested extensively for accuracy, reliability and clinical usefulness before it could be incorporated into routine care.
New treatment possibilities
Understanding the neural mechanisms behind relapse could eventually lead to new treatment targets.
Modern neuroscience techniques allow researchers to examine and manipulate specific groups of neurons in animal models. These tools can help scientists determine whether a particular brain circuit merely correlates with a behaviour or actually contributes to it.
If the BNST is shown to play a causal role in compulsive alcohol-seeking, it could become a target for future research into therapies designed to reduce relapse risk.
Such treatments would still be many steps away from clinical use, but identifying the relevant circuitry is an important part of understanding addiction.
Conclusion
The new findings offer a possible explanation for why some individuals may become particularly vulnerable to compulsive alcohol-seeking after a period of abstinence.
In mice, researchers observed increased activity in the BNST among animals that later showed stronger, aversion-resistant alcohol consumption. Crucially, the activity appeared before the animals were given access to alcohol, raising the possibility that it could eventually serve as a marker of relapse vulnerability.
However, the research is still at an early stage. Findings from mice cannot automatically be applied to humans, and BNST activity is not currently an established clinical test for predicting alcohol relapse.
Further human studies will be needed to determine whether the same neural pattern occurs in people and whether understanding it can lead to better prevention and treatment strategies for alcohol use disorder.