A glass of depression: the main thing is not to overdo it

The biochemical mechanism of the antidepressant effect of alcohol has been established

Oleg Lischuk, N+1

American scientists have found that a single intake of alcohol involves the same biochemical mechanism as "fast antidepressants" from the group of antagonists of glutamate NMDA receptors. The results of the work are published in the journal Nature Communications (Wolfe et al., FMRP regulates an ethanol-dependent shift in GABABR function and expression with rapid antidepressant properties).

Taking ethyl alcohol temporarily relieves the symptoms of depression, so people with this disease often resort to it for the purpose of self-medication. In many cases, this leads to alcohol abuse – its risk in major depressive disorder is more than doubled (and vice versa – alcohol abuse increases the risk of depression in about the same proportion). Chronic alcohol consumption, in turn, worsens the course of the disease, forming a vicious circle. At the same time, the biochemical mechanisms of the antidepressant effect of alcohol have not yet been known.

"Rapid antidepressants" such as ketamine, after a single injection, reduce the symptoms of depression within two hours, and this effect persists for two weeks. It has been shown that the long-term effect of NMDA receptor antagonists is associated with the activation of the mTOR signaling pathway in neurons (a mechanistic target of rapamycin), an important regulator of various intracellular processes, including protein synthesis. This activation requires a change in the expression and function of GABA receptors, which, instead of opening potassium channels, begin to increase the level of calcium in the dendrites of neurons. What provides such changes has also not been clear until now.

At the first stage of the experiments, the staff of the University of Texas at Austin made sure that the administration of alcohol to mice has an antidepressant and anti-anxiety effect similar to the effect of NMDA receptor antagonists, and also continues after the drug is excreted from the body. Experiments with cultures of hippocampal neurons taken half an hour after injection showed that alcohol, like "fast antidepressants", significantly increases the synthesis of the R2 subunit of GABA receptors, which is responsible for changing their functions.

Since the matrix RNA of GABA receptor subunits is present in the dendrites of neurons, scientists have suggested that the regulation of their synthesis occurs at the translation level. Experiments with the use of specific antibodies have shown that such a regulator is FMRP (a protein of mental retardation in the syndrome of brittle X chromosome), which reduces the activated, but not the basic synthesis of subunits. The introduction of alcohol or "fast antidepressants" reduced the level of FMRP.

In mice lacking the FMRP gene, no such regulation of the synthesis of GABA subunits was observed. They also lacked the biochemical effects of alcohol and NMDA receptor antagonists responsible for their antidepressant effect.

The sum of the data obtained indicates that both alcohol and "fast antidepressants" act by a similar biochemical mechanism, which depends on protein synthesis, is mediated by FMRP and is realized through synaptic plasticity provided by changes in the expression and functions of GABA receptors. According to researchers, this mechanism may play a key role in the development of alcohol abuse and dependence on it in major depressive disorder.

Portal "Eternal youth" http://vechnayamolodost.ru  30.09.2016