To Tackle Alcoholism, Scientists Turn to a Hormone Involved in Childbirth
A well-known hormone has dramatic effects on alcohol-dependent rats.
Maybe love is the answer to our spiritual woes, but the “love hormone,” oxytocin, may have even greater potential to heal some of society’s pressing health problems. New research in PLOS Biology points to the power of oxytocin to intervene in the vicious cycle of alcoholism by going straight to the brain to treat the disorder, which plagues millions of people.
Oxytocin is often called the love hormone, but it’s also a neuropeptide — a chemical signaling molecule released by the brain during particularly tender situations, from date night to hangouts with your dog. In the new study, it appears to have the power to temper alcohol abuse by changing how alcohol affects a crucial group of cells in the rat brain.
Lead author Brendan Tunstall, Ph.D., a post-doctoral fellow at the NIH’s National Institute on Drug Abuse, tells Inverse that he believes that oxytocin can become a full-blown treatment for alcoholism in humans. In fact, it’s already been tested on people; what his rat study shows it how it works.
“Preliminary studies in humans have already indicated that oxytocin may have beneficial effects in reducing physical signs of alcohol withdrawal and decreasing alcohol craving,” Tunstall tells Inverse.
“However, larger studies are needed to determine the potential therapeutic usefulness of intranasal oxytocin administration for alcohol use disorder.
Tunstall tested the effects of oxytocin on alcohol-dependent rats, whose brains showed similar responses to alcohol to the brains of humans with alcohol problems. Specifically, they looked at the response of the central nucleus of the amygdala, a key brain structure involved in alcohol addiction. This cluster of cells is a large population of neurons that show increased responses to gamma amminobutyric acid (GABA), a neurotransmitter, when faced with alcohol. It’s already established that both short-term and chronic alcohol use increased GABA signaling behavior in this area of the brain.
What Tunstall and his team wanted to find out was whether oxytocin would bring that chorus of hyperactive GABA signaling back to normal —and also alter the desire for alcohol in the process.
Sure enough, when the alcohol-dependent rats were given an intranasal dose of oxytocin and then given access to free drinks, their behavior changed. The rats, which once craved booze, stopped their compulsive drinking behavior after they got oxytocin doses. Meanwhile, the control rats, who were not dependent on alcohol, showed no difference in drinking after getting the oxytocin dose.
The alcohol-dependent rats still drank solutions of sugar and water, suggesting that oxytocin specifically impacted their preference for alcohol — not just tasty liquids in general. Those behavioral shifts, Tunstall found, were supported by what he saw when he looked the effect of oxytocin on GABA signaling in the rat brains.
In a series of earlier experiments, Tunstall’s team established that alcohol induced hyperactive GABA signaling, as they expected. But oxytocin seemed to dull alcohol’s effects on GABA signaling in alcohol-dependent rats. That dulling effect, they hypothesize, might be behind the changes in alcoholic behaviors they observe.
These results are promising, but they’re not a silver bullet for alcoholism, cautions Tunstall. His study only highlights oxytocin’s very specific effects on one category of neurons, so if dysregulation in that brain area is at the heart of alcohol use disorder, oxytocin may be a tonic. But if the problem lies elsewhere, it may not have the same effects.
Other studies have shown that oxytocin has the power to impact opioid use and obesity. Now, the new paper adds alcohol use to the list — and more importantly, shows us how it works. Going forward with tests on humans, that knowledge may help us combat substance abuse in the place where it really begins: the brain.
Abstract: Oxytocin administration has been reported to decrease consumption, withdrawal, and drug-seeking associated with several drugs of abuse and thus represents a promising pharmacological approach to treat drug addiction. We used an established rat model of alcohol dependence to investigate oxytocin’s effects on dependence-induced alcohol drinking, enhanced motivation for alcohol, and altered GABAergic transmission in the central nucleus of the amygdala (CeA). Intraperitoneal oxytocin administration blocked escalated alcohol drinking and the enhanced motivation for alcohol in alcohol-dependent but not nondependent rats. Intranasal oxytocin delivery fully replicated these effects. Intraperitoneal administration had minor but significant effects of reducing locomotion and intake of non-alcoholic palatable solutions, whereas intranasal oxytocin administration did not. In dependent rats, intracerebroventricular administration of oxytocin or the oxytocin receptor agonist PF-06655075, which does not cross the blood-brain barrier (i.e., it would not diffuse to the periphery), but not systemic administration of PF-06655075 (i.e., it would not reach the brain), decreased alcohol drinking. Administration of a peripherally restricted oxytocin receptor antagonist did not reverse the effect of intranasal oxytocin on alcohol drinking. Ex vivo electrophysiological recordings from CeA neurons indicated that oxytocin decreases evoked GABA transmission in nondependent but not in dependent rats, whereas oxytocin decreased the amplitude of spontaneous GABAergic responses in both groups. Oxytocin blocked the facilitatory effects of acute alcohol on GABA release in the CeA of dependent but not nondependent rats. Together, these results provide converging evidence that oxytocin specifically and selectively blocks the enhanced motivation for alcohol drinking that develops in alcohol dependence likely via a central mechanism that may result from altered oxytocin effects on CeA GABA transmission in alcohol dependence. Neuroadaptations in endogenous oxytocin signaling may provide a mechanism to further our understanding of alcohol use disorder.