Your Cerebellum May Dictate How Your Brain Handles Alcohol
Granule cells in the cerebellum may inhibit—or encourage—excessive drinking.
Posted August 31, 2016
A study published today offers new clues that help explain why some people are more inclined to be teetotalers—while others seem hardwired for heavy drinking. These groundbreaking findings show that alcohol doesn't interact the same way in every brain, which illuminates the neurobiology behind different drinking habits.
David Rossi, P.h.D., a professor of integrative physiology and neuroscience at Washington State University, and colleagues have pinpointed a specific cellular mechanism in the cerebellum (Latin for “little brain”) that strongly influences if an animal is likely to consume copious amounts of alcohol, or to drink in moderation.
The August 2016 study, ”Pharmacologically Counteracting a Phenotypic Difference in Cerebellar GABAA Receptor Response to Alcohol Prevents Excessive Alcohol Consumption in a High Alcohol-Consuming Rodent Genotype,” appears in the Journal of Neuroscience.
The mechanism reported by Rossi et al. appears to be like an on/off switch that drives patterns of alcohol consumption based on the activity of minuscule cerebellar neurons called granule cells. Attached to every granule cell are proteins called GABAA receptors which act like traffic cops directing electrical signals throughout the nervous system. (Cerebellar is the sister word to cerebral and means "Relating to or located in the cerebellum.")
Historically, neuroscientists have considered the cerebellum to be the seat of non-thinking motor activities such as coordinating and fine-tuning muscle movements. However, in recent years, a wide range of studies have found that the cerebellum plays a fundamental role in many of our cognitive, emotional, and creative processes. Now, it appears that the cerebellum may also play a role in reward processing, addiction, and alcohol abuse disorders.
"Whatever the Cerebellum Is doing, It's Doing a Lot of It."
My father, Richard Bergland, was a neuroscientist, neurosurgeon, and author of The Fabric of Mind (Viking). He was obsessed with the fact that the cerebellum is only 10% of total brain volume but houses well over 50% of your brain's total neurons.
Based on this disproportionate distribution of neurons, my Dad would say, "We don't know exactly what the cerebellum is doing. But whatever it's doing, it's doing a lot of it." If my father were alive today, I know he'd be thrilled by the new clues from Rossi that help solve some riddles of our mysterious and awe-inspiring little brain.
This new study on alcohol and the cerebellum was conducted by Rossi and colleagues at the Oregon Health and Science University and the U.S. Veterans Administration Portland Health Care System. The cerebellar mechanism they've unearthed offers a new target for pharmaceutical drug therapies that could be used to curb excessive drinking.
For this study, the researchers used two different inbred strains of mice—the "D2" and the "B6"—which are widely used in research because they happen to have different drinking phenotypes. This makes them all the more similar to individual human variations. The D2 mouse is a lightweight drinker who gets drunk quickly and becomes uncoordinated easily. After the equivalent of just one or two drinks, this strain of mouse has trouble fine-tuning the motor control necessary to stay on a rotating cylinder.
In a statement, Rossi said, "He [D2] won't drink much. At most, he'll have one or two drinks." On the other hand, the B6 mouse can guzzle three times more alcohol than the D2 mouse and stay balanced on the rotating cylinder like a Cirque du Soleil acrobat, even when it's highly intoxicated.
Additionally, the D2 mouse is a teetotaler. After just one or two drinks, it inherently wants to stop drinking. On the flip side, if given the opportunity, the B6 mouse will binge on alcohol. "It mirrors the human situation," said Rossi. "If you're sensitive to the motor-impairing effects of alcohol, you don't tend to drink much. If you're not sensitive, you drink more." In the cerebellum, granule cell inhibition leads to all the classic signs of being inebriated, such as, staggering, stumbling, slurred speech, etc.
When It Comes to Alcohol, Are You More of a D2 or B6 Type of Drinker?
The researchers found that in the D2 mouse the granule cells in the cerebellum are disrupted quickly. The subsequent impairment eliminates the drive to consume more alcohol. Conversely, when the granule cells are not easily impaired—as in the B6 mouse—the urge to drink alcohol excessively escalates into binge drinking.
This finding could help to explain why about half of those with alcohol abuse disorders are believed to have some type of genetically determined proclivity to abuse alcohol.
Until recently, the cellular and molecular mechanisms of the genetic influences on alcohol drinking behaviors have remained enigmatic. This study demonstrates that genetic differences in cerebellar granule cell GABAA receptor responses to recreational concentrations of alcohol may be the primary determinant of alcohol's impact on cerebellar processing. The good news is that pharmacologically modifying such responses has the power to alter alcohol consumption behaviors.
These findings reveal that the cerebellum is an important neuroanatomical region relating to alcohol consumption. They also add to a growing list of cognitive and emotional roles that the cerebellum may play in psychiatric diseases and drug abuse.
During their recent study, Rossi and colleagues also injected a drug called THIP into a specific subregion of the cerebellum in B6 mice. THIP activates the GABAA receptor. This recreated the effect that alcohol has on low drinking D2 mice. Interestingly, it ended up deterring the B6 mice from binge drinking but had little impact on their motor control.
Rossi believes these findings may have pinpointed specific new cerebellar targets that can be manipulated "to deter excessive alcohol consumption, and potentially with fewer side effects than other existing targets and brain circuits." The exact reasons for this remain somewhat of a mystery.
Because the cerebellum is most likely involved in many emotional and cognitive processes beyond motor coordination, Rossi hypothesizes that the specific subregion of the cerebellum they targeted with THIP could actually trigger the deterrent mechanism to drink less alcohol. Future research by Rossi and his team will explore this phenomenon in depth.
How Are Genetic Differences in the Cerebellum Linked to Alcoholism?
Liza Minnelli has vividly described the first time she drank alcohol in her late 20s at the notorious Trader Vic’s bar in the old Plaza Hotel. After an hour of drinking Hawaiian Mai Tai’s with a group of friends, other people at the table started dozing off. But, Minnelli was revved up and raring to go. She exclaimed, “Wow. I’ve arrived! This is how I should have been feeling my whole life. This is it! And that is because of the chemistry in my brain. I’m not kidding around. It really is about brain chemistry.”I am simpatico with what Minnelli describes above. I realized at boarding school that my body and brain responded differently to alcohol than most of my peers. My drinking buddies in prep school consisted of a small handful of classmates who, like me, seemed to have a proverbial “wooden leg.” We could consume liters of Vodka and pretend to be stone cold sober in order to pass the mandatory face check each night with our dormitory housemaster. None of us ever got busted.
Later in life, I realized that alcohol was like rocket fuel for me on the dance floor. Instead of alcohol making me drowsy or discombobulated, drinking Heinekens made me energized and gave me a feeling of superfluidity—which I describe as existing without any friction or viscosity.
While out dancing, I could literally “sip and twirl” until the predawn hours of the morning. Most people (including the D2 mouse) would be passed out in the corner if they consumed half as much alcohol. To be honest, I’ve never met anyone who can drink as much as me and stay standing. This is not something I'm proud of. I see this genetic predisposition more as a curse than a blessing, obviously.
I have a hypothesis that there may be a correlation between my athletic prowess and my ability to binge drink. Although this is pure conjecture, I have a hunch that if there is, in fact, a link between granule cells in the cerebellum and binge drinking, it would make sense that having a highly developed cerebellum through athletic conditioning might make someone a more proficient drinker. Again, this is speculative conjecture and just an educated guess on my part.
Conclusion: The Cerebellum May Play a Significant Role in All Types of Substance Abuse and Addiction
In both sport and life, I’ve always considered myself a human lab rat and have filtered my life experiences through the lens of neuroscientific empirical evidence. That said, if I were a mouse in the latest study, I have no doubt that I would test like the B6 strain. The latest research suggests that the roots of addiction and alcoholism may be seated in the cerebellum, which I find both fascinating and kismet.
In an editorial response to this latest research, “Cerebellar Inhibition Reduces Alcohol Consumption,” Teresa Esch, Ph.D., et al. from the Journal of Neuroscience conclude,
“Susceptibility to alcohol abuse has a strong genetic component. Some of this susceptibility may result from genetic influences on physiological and behavioral responses to alcohol. For example, people with a family history of alcohol abuse are able to consume more alcohol without experiencing motor impairment than people with no such family history . . . Studies have revealed that alcohol has opposite effects on tonic currents mediated by GABAA receptors (GABAARs) in cerebellar granule cells.
These results suggest that genetic differences in the effects of alcohol on granule cell inhibition influence the amount of alcohol consumed. Additional experiments showed that these effects were likely mediated by reduced excitation of Purkinje cells, the sole output neurons of the cerebellar cortex. This work adds to mounting evidence that cerebellar circuits contribute to reward processing and addiction—an exciting direction for new research.”
Stay tuned for more on this fascinating topic! If you'd like to read more about the cerebellum, check out my previous Psychology Today blog posts,
- "The Neuroscience of Binge Drinking"
- "Michael Phelps' Heroic Journey Goes Far Beyond Gold Medals"
- "Neuroscience Suggests That We're All "Wired" for Addiction"
- "Harvard Research Shows How the Cerebellum Regulates Thoughts"
- "Enhanced Cerebellum Connectivity Boosts Creative Capacity"
- "Purkinje Cells Burst to Life With State-Dependent Excitation"
- "5 Reasons the Cerebellum Is Key to Thriving in a Digital Age"
- "The Cerebellum Many Be the Seat of Creativity"
- "Cerebellum Damage May Be the Root of PTSD in Combat Veterans"
- "More Research Links Autism and the Cerebellum"
- "The Cerebellum Deeply Influences Our Thoughts and Emotions"
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