(ORDO NEWS) — Russian scientists discovered the phenomenon of despair in fresh zebrafish and zebrafish and found that depression is an older mechanism than previously thought: as much as 340 million years.
A group of Russian biologists from the Ural Federal and St. Petersburg State Universities, as well as from the National Medical Research Center named after Almazova, with the support of her colleagues from Moscow, Novosibirsk, China and Brazil, hanging danios rerio (or zebradanio) by the tail of freshwater fish, first discovered a “despair phenomenon” in them and tested drugs for treating depression on this model. The study is published in the Journal of Neuroscience Methods.
Danio rerio belongs to the species of small transparent freshwater ray-fin fish from the family of cyprinids. This is not only a popular fish for breeding in aquariums, but also a common – economical and simple – version of the model organism in biological research. Among other things, these fish have a complex nervous system, are distinguished by endurance and survival, as well as rapid development (adults form in just three months).
“Along with the nematode worm, the Drosophila fly, mouse and human, the zebra danio is a member of the“ elite club ”of fully genetically identified species and is very convenient for genetic manipulations and the creation of mutant specimens. And since the egg, larva and adult zebra danio are transparent, this allows you to visually observe the effects of various drugs, to test them at the level not of individual cells and tissues, but of the whole organism. At zebra danio possible to test drugs and much more likely to find one that will slow down the disturbances in the brain and its fish nervous system”, – reported in the press release on the website of the Ural Federal University.
The authors of the study, in their own words, presented a new behavioral paradigm using the zebrafish immobilization test. The experiment consisted in the fact that the tails of these fish “blocked” inside the spongy material, leaving the cranial part free to move, and vertically placed the zebrafish in a glass with the classic antidepressants – amitriptyline (included in the group of tricyclic compounds; a derivative of dibenzo cyclohepta dine) or sertraline (an antidepressant from groups of selective serotonin reuptake inhibitors). In this state, the fish spent five minutes.
To test the model, we also used low-voltage electric shock, anxiety pheromone, and the anxiolytic drug benzodiazepine (phenazepam). Then, using video tracking, scientists evaluated the frequency and total amplitude of the zebrafish, the duration of their fading, and other types of activity of the front of the body.
The results showed that both electric shock and signal pheromone reduced the activity of fish, antidepressants, on the contrary, increased it (this indicates a decrease in despair), and phenazepam did not cause any changes in behavior.
On the whole, five-minute immobilization of fish increased their serotonin turnover in their brain (it is closely associated with depression and emotions in humans), while electric shock before the test increased the production of both serotonin and dopamine. A preliminary exposure to the antidepressants sertraline and amitriptyline lowered both ratios.
“First, we first discovered the phenomenon of despair in zebra danio fish. Secondly, it was determined that the use of antidepressants in relation to zebra danio in despair leads to approximately the same changes as in the case of exposure to rodents and people with antidepressants. Thus, we “pushed back” the model of despair based on learned helplessness by 340 million years: after all, the first jaw fish appeared during evolution 400 million years ago, and rodents 60 million years ago,” study leaders Alan Kaloyev from Ural Federal University explain and Konstantin Demin from the Institute of Translational Biomedicine, St. Petersburg State University.
According to the authors of the study, collectively, their work offers an immobilization test as a potentially effective protocol for assessing behavior associated with stress or despair, and subsequent testing of antidepressants, which previously had traditionally been tested on mouse models (rodents are also suspended by the tail, but only they they resist less, and under the influence of drugs show greater activity).
“Given that fish and humans are genetically similar to each other by 70 percent, we have made the search for potential biological targets for antidepressants much less complicated and expensive than when working with rodents. Using zebra danio fish and treating them with various substances, science will quickly find, test and select new, more advanced drugs against depression – the most massive, debilitating and disabling brain disease that affects nearly ten percent of people, many of whom with ineffective treatment commit suicide”.
Recently, Australian biologists have identified neural circuits that allow fish to sense the flow of water, and their colleagues from the United States first discovered a fish that lives in deep water and carries offspring in the mouth.
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