Your brain on a bender

September 7, 2021

Written by: Greer Prettyman

With the start of the college semester and football season, fall can be a prime time for heavy consumption of alcohol. No matter the season, many people engage in binge drinking, which is defined as alcohol consumption that brings someone’s blood alcohol concentration (BAC) to 0.08% or higher¹. Binge drinking is associated with many health and safety risks, even in people who do not meet the qualifications to be diagnosed with an alcohol use disorder.

People who want help reducing their binge drinking currently have several options. Counseling, therapy, and programs like alcoholics anonymous (AA) can help to target the behaviors and environmental factors that lead to drinking. There are also several FDA-approved medications to help with alcohol abuse². Some, like disulifiram, enhance negative effects of alcohol, making someone sick if they drink even a little bit so that drinking becomes unpleasant. Others, like naltrexone and acamprosate, reduce the rewarding effects of alcohol, making it less of a positive experience and therefore reducing a person’s motivation to drink. Another chemical that has recently gained attention as a potential therapeutic for heavy drinking is oxytocin³.

Oxytocin is a hormone and neuropeptide that is produced in the hypothalamus in the brain. You may have heard of oxytocin referred to as a “love hormone” due to its roles in both sexual activity and mother-baby bonding. Oxytocin is synthesized and released from neurons in the periventricular nucleus (PVN) and supraoptic nucleus (SON) of the hypothalamus. Receptors for oxytocin are expressed throughout the body, regulating processes like arousal and lactation. Oxytocin receptors in the brain, including in the prefrontal cortex and the amygdala, are responsible for regulating proper social and emotional behaviors. 

Physicians and researchers have examined the potential therapeutic uses of oxytocin by administering extra oxytocin to people in the form of a nasal spray. Oxytocin administered in this way can help to reduce cravings for alcohol and ameliorate withdrawal symptoms. However, the mechanism by which oxytocin impacts the desire to drink was not well understood³. Even when drugs are administered in the nose, it is hard to get the drug across the blood brain barrier— the protective layer that keeps germs and harmful substances from getting into the brain. Some scientists hypothesized that exogenous oxytocin (in the form of a spray) could be reducing drinking by activating endogenous (natural) oxytocin release. 

Many of the situations that lead to binge drinking seem uniquely human. Mice don’t go to fraternity parties, after all. In some research, however, animal models can be used to study excessive alcohol consumption and learn about potential therapeutic techniques to reduce drinking. In one such study, scientists used a “drinking in the dark” paradigm to create binge-like behaviors in mice. At night when their cage is dark, mice were given access to a bottle of 20% ethanol for 2 hours, essentially creating the mouse equivalent of a dimly lit bar. Under these conditions mice will drink until their BAC is > 1%, creating a model that scientists can use to study drinking behavior⁴. 

Researchers used this mouse model to test the hypothesis that endogenous oxytocin release reduced drinking by directly activating oxytocin neurons in the hypothalamus during the binge drinking paradigm⁵. As expected, mice whose PVN neurons were activated drank significantly less than mice in the control group. When the animals were also given a drug that blocked oxytocin receptors in the brain prior to the activation of these neurons, the reduction in drinking disappeared. This was not the case when oxytocin receptors in the body were blocked instead. Therefore, the scientists concluded that oxytocin release onto receptors in the brain underlies reduced alcohol consumption. Other research has pointed to downstream effects of oxytocin on a brain region called the central amygdala, which may reduce motivation to drink⁶. While the specifics of this circuit are still being investigated, knowing which oxytocin receptors can be activated to reduce binge-like behavior gives researchers a clue into how to develop new therapeutic techniques to help with unwanted drinking. 

If you have noticed that you are drinking more than you did before 2020, you’re not alone. Up to 60% of Americans have reported an increase in alcohol consumption during the COVID-19 pandemic⁷. You might look to your own oxytocin neurons if you’re hoping to cut back on evening cocktails. Oxytocin is released when you interact with others, listen to music, share a meal, pet animals, exercise, and cuddle. In addition to boosting your mood, trying one of these activities can help you to get past a craving without having too much to drink. 

References:

1. Center for Disease Control https://www.cdc.gov/alcohol/fact-sheets/binge-drinking.htm
2. Swift, R. M., & Aston, E. R. (2015). Pharmacotherapy for alcohol use disorder: current and emerging therapies. Harvard review of psychiatry. 23(2), 122–133. 
3. Ryabinin, A.E. & Fulenwider, H.D. (2021). Alcohol and oxytocin: Scrutinizing the relationship. Neuroscience & Biobehavioral Reviews. 127, 852-864.
4. Rhodes JS, Best K, Belknap JK, Finn DA, Crabbe JC. (2005) Evaluation of a simple model of ethanol drinking to intoxication in C57BL/6J mice. Physiol Behav. 31;84(1):53-63. 
5. King, C.E., Griffin, W.C., Lopez, M.F. et al. (2021). Activation of hypothalamic oxytocin neurons reduces binge-like alcohol drinking through signaling at central oxytocin receptors. Neuropsychopharmacol. Online ahead of print.
6. Tunstall BJ, Kirson D, Zallar LJ,  et al. (2019). Oxytocin blocks enhanced motivation for alcohol in alcohol dependence and blocks alcohol effects on GABAergic transmission in the central amygdala. PLoS Biol. 17(4):e2006421.
7. Grossman ER, Benjamin-Neelon SE, Sonnenschein S. (2020). Alcohol Consumption during the COVID-19 Pandemic: A Cross-Sectional Survey of US Adults. Int J Environ Res Public Health. 17(24):9189.

Cover Photo by Polina Tankilevitch from Pexels