Oxytocin, a brain peptide that is widely known for its role in love and bonding, may hold potential for helping individuals overcome alcohol addiction. In a collaborative study with the National Institute on Drug Abuse (NIDA), scientists at Scripps Research discovered that oxytocin blocked enhanced drinking in alcohol-dependent rats, concluding that targeting the oxytocin system may be a successful pharmaceutical approach for treating alcohol-use disorder.
The study appears in the April 16 issue of PLOS Biology.
“Because oxytocin is already produced in your brain, is generally well-tolerated as a treatment, and is approved by the FDA for use in humans, it has lot of potential for alcohol addiction,” says Dean Kirson, PhD, co-lead author of the study and a researcher in the laboratory of Marisa Roberto, PhD, a professor of neuroscience at Scripps Research. “We are cautiously optimistic that this research may lead to the development of new treatments for alcohol addiction that could help millions of people worldwide.”
Alcohol-use disorder is a chronic relapsing brain disease characterized by an impaired ability to stop or control alcohol use despite adverse social, occupational or health consequences. With such enormous impacts on families and society, a great need exists for new solutions to combat the disease.
In the new study, the Scripps Research-NIDA team tested the hypothesis that oxytocin administration could normalize the maladaptive brain changes that occur in alcohol dependence, thereby reducing alcohol drinking in an established rat model of alcohol dependence. The authors investigated oxytocin’s effects on dependence-induced alcohol consumption and the altered chemical signaling in the central nucleus of the amygdala, a key brain region associated with stress and addiction.
The experiments demonstrated that when oxytocin is administered systemically, intranasally or into the brain, it blocks excess drinking that develops in alcohol-dependent rats, but not in normal, nondependent rats. Moreover, oxytocin blocked signaling by the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Taken together, the results provide evidence that oxytocin likely blocks enhanced drinking by altering GABA transmission in the amygdala, and that aberrations in the oxytocin system may underlie alcohol use disorder. Targeting this system, possibly by administering oxytocin via a nasal spray, may be a promising therapeutic approach for people with alcohol-use disorder, the team found.
The Roberto laboratory collaborated on the study with Brendan Tunstall, PhD, Leandro Vendruscolo, PhD, and George Koob, PhD, all of whom are experts in the field of addiction at NIDA, one of the centers of the National Institutes of Health. Koob also is co-founder of Scripps Research’s Pearson Center for Alcoholism and Addiction Research, which is focused on discovering novel treatments for substance abuse disorders.
The Roberto and Koob laboratories have had longstanding collaborations on a variety of topics related to addiction. They came together on this research because each had been independently investigating the role of oxytocin and addiction, but in different ways. The Scripps Research scientists focused on synaptic effects of oxytocin and alcohol in the brain, whereas NIDA collaborators were studying the behavioral effects of oxytocin in decreasing dependence-induced drinking. Both laboratories had garnered exciting data and decided to work together to investigate mechanism of action.
“Oxytocin has been reported to decrease consumption, withdrawal and drug-seeking behavior associated with several drugs of abuse, including alcohol, and now we are a step closer to fully understanding why,” Roberto says. “Alcohol-use disorder is a global public health issue that demands new treatment approaches. Looking ahead, we plan to continue to explore oxytocin’s role in addiction with the hope that we can illuminate new and better options to address the disease.”
Additional authors of the study, “Oxytocin blocks enhanced motivation for alcohol in alcohol dependence and blocks alcohol effects on GABAergic transmission in the central amygdala,” include Lia J. Zallar, Sam A. McConnell, Chelsea P. Ho, Janaina C. M. Vendruscolo of NIDA, Maurice Manning of University of Toledo College of Medicine and Life Sciences; Christopher S. Oleata and Sophia Khom of Scripps Research; Mary R. Lee and Lorenzo Leggio of NIAAA/NIDA.The study was supported by National Institute on Drug Abuse-Intramural Research Program and the National Institutes of Health (grants F32 AA02526, AA015566, AA017447, P60 AA006420 and K99 AA026638).