Alcohol use disorder (AUD) and general anxiety disorder (ANX) have become more of a hot-button issue and addiction biology is still struggling to isolate the genetic proclivities if any of these and other disorders. Which as of now have very few effective long term treatments. It also is unable to answer the question of why do certain people who have perhaps the same exposure to both stress and access to alcohol fail to develop severe addiction or reoccurring symptoms of stress. It probably comes as no surprise that humans are well-documented in having a connection between stress and these types of disorders or that the two coincide or are comorbid with one another. Meaning people that experience one have a higher rate than the average of experiencing the other. Furthermore there does seem to be some epidemiological basis for these tendencies. This particular study has looked at the effect of stress on rats to their likelihood to develop anxiety and increased self administration of alcohol to see if there’s a physiological mechanism within the brain that accounts for this correlation.
Rats are social creatures and like many animals have a hierarchical system with in-groups and out-groups, dominant and more subservient memberships. But rats like people can feel shame or embarrassment when they are dominated by larger, stronger members. Particularly ones outside of their familial group. Researchers experiment with rats call this phenomena “social defeat stress” or SDS it’s a cocktail of fear and mortification that rats experience when they’ve been bested or subdued by another rat. Not only does the subdued rat experience trauma but just like with people who are privy to traumatic events but not necessarily directly or physically harmed by it can carry with them residual stress as a result. (PTSD in First Responders for example.) Other rats who witness this also experience a similar albeit slightly less severe level of stress. So scientists came up with an experiment in which they would pair one smaller breed of rat with a much larger species called Wister rats to force them into confrontations that they couldn’t win with a familiar not aggressive housemates watching from behind a transparent divider. They repeated this process for 10 minutes a day over and over for weeks all the while recording their stress levels and alcohol intake both the defeated rat and the witness rat demonstrated following each successive negative encounter. After the experiment was over the rats were divided up into groups based on the perceived toll these interactions had on them. Ones that did not show signs of excess stress behavior were considered resilient whereas other more effected rats were labelled as susceptible. They did this by first acclimating the rats to alcohol prior to any kind of stressful engagement and then monitoring their behaviour while in an elevated plus (+) shaped maze or EPM. Rats that are experiencing stress behave more timid and frightful as one might expect. They’re less likely to play and be adventurous so a maze they are otherwise accustomed to is actually an excellent measure of the rats emotional state. Using an above ground plus shaped maze with half open and half closed sections researchers can determined by the amount of time the rat would spend secluded in hiding within the covered sections versus more boldly exploring the open sections what level of stress they had internalized. Blood samples were also drawn to measure the levels of corticosterone a known stress hormone. The rats were given access to a supply of alcohol and of course this included a test group of rats that had the same exposure to alcohol but without the stress of being regularly dominated.
After the experiment researchers studied the rat’s brain for physiological changes. Particularly in the area of the amygdala (AMD) an important part of the limbic system responsible for emotion, memory and our fight or flight response which is known for the regulation of stress both in rats and humans. Activity in the amygdala has also been found to be key in the presence of anxiety and alcohol disorders.
What researchers found was that roughly half of all the rats that have been exposed to SDS had increased their observable anxiety-like behavior up to 2 weeks after their last encounters with an aggressor with around 11% of the same group escalated their alcohol self-administration. But not only was there a positive correlation between the effects of stress on the consumption of alcohol in the susceptible rat subpopulations but also in the witness rats who were traumatized by proxy. These sample rats that were labelled as comorbid also had up-regulated amounts of oxytocin (OXT) and vasopressin (AVP) in their brains. These neurochemicals called peptides are significant in stress response and mediation. They even noticed that stressed rats lost weight compared to their more resilient and control group counterparts. These gene expressions support previous findings including the injection of vasopressin into the amygdala to simulate a stress response. Interestingly, oxytocin had been previously considered as a treatment for trauma patients because of its perceived anxiolytic effects. Oxytocin is formed mainly in the hypothalamus of the brain and it is conceivable that its presence in the amygdala functions either due to proximity or as a regulatory framework or counterbalance in the presence of stress hormones. These findings support the hypothesis of the study as well as correlations to similar effects in humans including the minority percentage that will continue to abuse alcohol even after the presence of stress. This data may highlight the underpinning of a mechanism in the brain that identifies a connection between sensitivity to stress and propensity for alcohol abuse.
References:
Asratian A, Augier E, Augier G, Barbier E, Barchiesi R, Chanthongdee K, Coppola A, Domi E, Gobbo F, Heilig M, Holm L, Toivainen S, Xu L. (Jan 2021)“Stress-induced escalation of alcohol self-administration, anxiety-like behavior, and elevated amygdala Avp expression in a susceptible subpopulation of rats.”Addiction Biology. 2021;26:e13009. https://doi.org/10.1111/adb.13009

-MS