A team of neuroscientists from Linköping University in Sweden published a study on Tuesday in Addiction Biology examining how social stress impacts the development of anxiety-like behaviors and alcohol consumption in rats.
The authors note that in humans, the correlation between alcohol use disorders and anxiety disorders is well established, with more severe symptoms than either condition alone. Stress, including social stress, is a known risk factor for both conditions, but there is high variability in susceptibility to psychiatric conditions following exposure to stress. For some people, witnessing distressing events occur to others may increase the likelihood of developing an anxiety disorder or alcohol use disorder.
Given this comorbidity in humans, the researchers hoped to determine whether a common mechanism promotes stress-induced alcohol self-administration and anxiety-like behaviors in rats.
Rodent models of stress and alcohol consumption
Social stress was modeled using the social defeat stress (SDS) paradigm in which an animal is repeatedly attacked and subordinated by another animal of the same species. The SDS paradigm is known to be associated with increased anxiety-like behaviors, but studies attempting to determine the relationship between SDS and alcohol consumption have produced mixed results.
To differentiate the physiological and psychological effects of the attacks in the SDS paradigm, a second rat was added to the model that would witness the attack on the first rat. Such rodent models of witness stress have been linked to anxiety-like behaviors, but this paper marks the first attempt to quantify the effect of witness stress on alcohol consumption in rats.
Rats in the study were trained to self-administer alcohol for two to three months, after which they were exposed to either social defeat stress or witness stress for a ten day period. After a week-long rest period, the rats were evaluated for anxiety-like behaviors using an elevated plus maze (EPM) test.
In the EPM test (pictured), an animal may spend time navigating the closed and open arms of the maze. An animal that spends relatively more time in the closed arms of the maze is considered to exhibit more anxiety-like behaviors.
The researchers found an increase in anxiety-like behaviors and alcohol consumption in both the groups exposed to SDS and witness stress, but the increase wasn’t universal in either group. In fact, both groups had mice that could be categorized as either comorbid (increased alcohol intake and anxiety-like behaviors relative to a non-stressed control) or resilient (no such increases).
Could genetic factors account for the resilience of some rats to stress?
The team next sought to establish a mechanism to account for the difference between comorbid and resilient rat populations. Their search was focused on the amygdala, a structure in the limbic system with a role in emotions and memory; the laboratory’s previous work suggests a role for the the amygdala in the link between alcohol consumption and anxiety. Gene expression within the amygdala was compared across the different groups. Transcripts for Avp, which codes for the hormone vasopressin, were found at higher levels in the amygdalas of comorbid rats.
Previous studies have linked Avp to alcohol consumption following stress as well as to emotional regulation. The present study suggests that higher Avp expression levels in the amygdala may predispose rats to comorbid anxiety like behaviors and alcohol consumption following social defeat stress or witness stress.
This study on rats can not be used to draw conclusions about the comorbidity of alcohol use disorders and anxiety disorders in humans; biological differences aside, the stressors people face and their behavioral responses to those stressors are far more complex than what can be replicated on laboratory animals. Still, as researchers continue to disentangle the genetic and environmental factors underlying the wide variation in human resilience, this paper presents a promising target for future inquiry.