Stress Addiction

It is not uncommon for one to think of stress and drug abuse as directly proportional since it is common sense that the more stressed an individual is, the more drugs he/she will intake. We are intuitively primed to think that way by media outlets, including movies and shows that = emphasize a relationship between drug abuse and stress. However, a definite biological link between stress and drug addiction has yet to be discovered. Neurologist Klaus Miczek and his team have devoted their scientific studies in an attempt to discover the molecular cause of stress induced addiction in hopes of uncovering therapeutic outcomes.

When asked about the source of his inspiration, Professor Miczek states, “It would take a good afternoon to answer all the reasons that I do what I do.” However, he does credit his personal experience in Berlin, Germany. “I grew up in Berlin, Germany, which was in the immediate post-war period. There was a lot of social stress when soviet tanks came rolling down the street and confronted civilians. That was as stressful as it could be.” He characterizes himself as one of those who were resilient and did not succumb to the morbid reality of the time. “I survived,” he asserts.

For decades, Professor Miczek studied this phenomenon. For years, Beacon Hall at Boston Avenue was a home for his scientific exploration. The wet lab houses rodent samples, which are the subject of his tests due to the invasive nature of his experiments. Within this lab, Professor Miczeck and his team would inflict various types of social stress of different forms and subsequently analyze and observe their influence on drug intake. The rodent samples are given full control of self-administering drug consumption.

While the use of rodent models is essential for ethical reasons, it has proven to be a limitation at times as results seem to lack translational significance. For instance, when it comes to the neuropeptide corticotropin releasing factor (CRF). In collaboration with Herb Covington, a research assistant professor at the time, Professor Miczek and his team were able to draw a link between CRF and stress-induced drug ingestion. It was found that the craving for drugs can be terminated in rodents when the CRF receptors are blocked. However, when the findings were translated into humans, the drugs used to block the receptors were deemed incompatible with human biology, causing side effects. “Obviously, we are not eager to find a cure for drinking in mice and rats,” exclaims Professor Miczek.

For the past year, Professor Miczek has been working in collaboration with researchers from Northeastern University, Maclean Hospital, and other companies invested in what he calls “an ambitious project.”

The Miczek lab conducts three major pre-clinical projects: 1-) interaction between alcohol, aggression, and social stress; 2-) endocannabinoids and drug abuse; 3-) cocaine and its interaction with stress.

Interaction between alcohol, aggression, and social stress

In this project, Professor Miczek uses rodent subjects that are long-term dependents of alcohol and hence drink excessively and prefer alcohol over water. They then introduce chemical agents created by the medicinal chemist Alexandros Makriyannis of Northeastern. These compounds are intended to selectively reduce alcohol. The goal of this project is to alleviate withdrawal symptoms and prevent relapse.

Professor Miczek refers to this project as a puzzle as he tries to “interfere in the brain-based stress system to prevent the stress escalation of alcohol consumption.” An interesting finding of this experiment is that under low or moderate levels of alcohol consumption in mice, we can mimic alcohol-induced heightened violent behavior in humans. As a result, they are capable of characterizing individuals prone to alcohol escalation of aggression through their neurobiological characteristics.

Endocannabinoids and drug abuse

The study of the correlation between endocannabinoids and drug abuse is relatively new to the lab. Professor Miczek describes it as a “promising” and “ambitious” new trajectory. By his definition, cannabinoids are the endogenous chemicals that correspond to the plant product of cannabis, marijuana, where the active ingredient is tetrahydrocannabinol (THC).

The aim of this project is to target the receptors in which endocannabinoids act in an attempt to buffer their impact. With NIH’s support for five consecutive years, Professor Miczek and his team look forward to exploring the realm of endocannabinoids.

Cocaine and its interaction with stress

As the oldest Miczek lab, the study of cocaine and its relation to stress is the most refined project. The project aims to study psychomotor stimulants such as amphetamine and cocaine and how they interact with “stress conditions.”

To analyze the interaction of cocaine and stress, individual rodents are exposed to social stress. This can be of various forms, including the direct confrontation with an aggressive opponent or through mere proximity to the aggressive opponent. In a direct confrontation, the aggressive opponent is introduced into the rodent’s cage, and violent altercations arise. While in the case of proximity, an aggressive opponent neighbors the cage of the victim rodent. Researchers have found that victims of social stress are prone to consume drugs at a higher rate than control samples.

Psychomotor stimulants generally induce a cascade of endocrine activity in certain brain regions. In his lab, Professor Miczek and his teams were able to identify these regions. Crediting new tools and technological advancements, the team was able to chemogenetically block the stress effect and reduce the escalation of cocaine ingestion.

Female vs. Male

A major limitation to the legitimacy of psychology experiments is their primary focus on male models. For centuries, males were construed as the prototype of behavior and biology. However, since this is obviously not fundamentally true, Professor Miczek has taken it upon himself to implement the use of female rodent models. “One would think that researchers would have had more interest in females, but they were always an outlier in this aspect,” says Professor Miczek.

For the past year, Professor Miczek has been exploring the difference between female and male models. He soon realized that the two are drastically different neurobiologically. He states that the difference “is not just in the shades of grey; it’s actually in the kind.” Some of the most significant findings are that females are more susceptible to relapse. Other findings include that female-to-female interaction can trigger extreme stress levels, thus exasperate their craving for drugs. Additionally, female gene expression patterns in various brain areas are substantially different than that of males. The team of researchers aims to at some point be able to manipulate these areas to suppress the stress induced craving for alcohol and other drugs.

“Females historically lagged behind males when it comes to drug abuse, but nowadays, they are catching up,” states Professor Miczek, “a nasty trend.” He continues,“ one would not like for them to catch up to males in this regard.”

Aside from their salient social impact on the genders, drug addictions pose a great danger when it comes to quarantining. While he has not conducted research on the topic, Professor Miczek predicts a surge in the relapse of alcohol and drug consumption, synonymous with the predicted surge in domestic violence cases. He classifies quarantining and other social restrictions of the pandemic as a form of social stress that can trigger heightened alcohol drinking and subsequently heightening aggressiveness that can lead to domestic violence. Additionally, he mentions that COVID’s possible impact on the expansive opioid crisis in the US, concluding that the progress of the lab is essential for the social and physical well-being of many.