Citizens are alcoholics! Block the stress hormone!
Scientists at the Scripps Research Institute (La Jolla, California), working under the guidance of Professor Marisa Roberto, demonstrated in an animal model that the stress hormone corticoliberin plays a key role in the development and maintenance of alcohol dependence. Chemical blocking of this factor eliminates the symptoms of addiction, which makes it possible to consider corticoliberin a potential target of new drugs for the treatment of alcoholism.
The data obtained as a result of more than six years of work are published in the preliminary on-line version of the journal Biological Psychiatry in the article "Corticotropin Releasing Factor–Induced Amygdala Gamma-Aminobutyric Acid Release Plays a Key Role in Alcohol Dependence".
The results of earlier studies showed the involvement of corticoliberin in the development of alcohol dependence, but the effectiveness of its blocking was demonstrated only for a single administration of large doses of the antagonist. The authors of this work tested three different types of corticoliberin receptor antagonists in experiments on rat tissues. All three compounds proved to be effective; in addition, after regular (for 23 days) administration of one of the drugs, alcoholic rats voluntarily switched from heavy drinking to moderate drinking.
Alcoholism is a chronic disease characterized by an irresistible attraction to alcohol and loss of control over the use of alcoholic beverages. Alcohol addiction has a negative impact not only on the lives of individuals suffering from it and their families, but also on society as a whole. The cause of about a third of deaths as a result of road accidents is drunk driving, and the costs of medical care, directly and indirectly related to alcohol abuse, amount to hundreds of billions of dollars annually in the United States alone.
The hormone corticoliberin is involved in the development of the body's response to stress. Initially, it was found only in the hypothalamus, but later studies have revealed its presence in other regions of the brain, including the pituitary gland, where it stimulates the secretion of corticotropin and other biologically active substances, and in the amygdala, involved in the formation of a state of increased anxiety, withdrawal syndrome and characteristic alcohol addiction cravings.
To confirm the role of amygdala corticoliberin in the development of alcohol dependence, the authors used a multi-pronged approach, including the use of electrophysiological methods not previously used to study this problem.
The results of experiments conducted at the cellular level showed that corticoliberin, like alcohol, increases the strength of interneuronal inhibitory synapses. This effect developed as a result of the release of gamma-aminobutyric acid (GABA), a neurotransmitter that plays an important role in regulating the excitability of neurons.
After that, the authors tested on brain slices of rats the possibility of blocking the effects of alcohol and corticoliberin with the help of three different corticoliberin receptor antagonists: the antidepressant antalarmin (antalarmin, from alarm – alarm), which is currently undergoing clinical trials, and two substances under the conditional names NIH-3 and R121919. All three compounds suppressed GABA-mediated reactions and eliminated the effects of alcohol.
In addition, for 23 days they injected R121919 into the brains of rats who had unlimited access to alcohol, which under normal conditions inevitably leads to the development of alcoholism in animals. As a result, alcoholic rats receiving injections of R121919 behaved in the same way as normal animals, that is, instead of drinking a large amount of alcohol, as dependent animals usually do, they were limited to small doses. According to Professor Roberto, this observation indicates that increased activation of the corticoliberin-mediated mechanism leads to excessive alcohol consumption, which is a symptom of addiction. In other words, long-term suppression of the effects of corticoliberin can prevent alcohol abuse even in favorable conditions.
It is also important that animals not only did not develop tolerance to R121919, but, on the contrary, over time they became more sensitive to its suppressive effect. This indicates the great potential of R121919 as a promising drug therapy for alcohol dependence.
Roberto also notes that another interesting aspect of this work is that the results indicate the possibility of a psychological relationship between stress-associated behavioral features and emotional disorders (such as anxiety, depression) and the development of alcohol dependence.
Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of the Scripps Research Institute: Team Finds Stress Hormone Key to Alcohol Dependence.
02.02.2010