Disabling neurons in the thalamus of mice forced addicts to forget about the morphine

American scientists have discovered the key area of the brain responsible for the formation of associations between environmental factors and drugs in dependent. It appeared to be paraventricular nucleus of the thalamus: inhibition of its connections with the amygdala and adjacent the core have resulted in morphine-dependent mice or couldn’t get used to the room in which they were given drugs, either quickly lost interest in it. The detected relationships can be used to develop methods of treatment of dependencies — at least opioid, write the scientists in the journal Neuron.

In the formation of dependency a key role is played by the relationship between the object of addiction and accompanying feelings: in drug addiction, for example, the consumption of the substance associated with pleasure, and the absence of substances with a withdrawal syndrome of varying severity. There is such a connection very quickly, although not always leads to addiction: a role play third-party factors that can activate compensatory mechanisms prevent that the dependency is still there.

Intermediate there may be environmental factors: if you already formed a link between the object of addiction and the resulting sensations such factors may increase the desire. So, for example, dependent on tobacco connected the desire to smoke and the smell of cigarette smoke or the sight of smokers. The effect of this intermediate is one of the most effective ways of getting rid of dependencies, but it does not always work equally efficiently: in order to stop link what is happening around, with the object of addiction and pleasure, which leads to its consumption, not only to get rid of external factors.

On the other hand, can help target the memories, which bind external factors and dependence, especially at the level of the brain. Scientists from Stanford University under the leadership of Saoca Chen (Chen Xiaoke) suggested that the key role in the formation of such memories can play paraventricular nucleus of the thalamus (projection neurons it connects its participating subject departments: an adjacent nucleus and amygdala) and it is necessary to target for getting rid of addiction.

To confirm this, scientists conducted an experiment on mice. For this they used a classic paradigm of conditional preferences place. The mice were let into a cage with two rooms and after they pick one, they injected the saline and kept there for 45 minutes for four days every day. After that, mice were injected with morphine and repeated the procedure, but with another room. After a period of habituation, mice were allowed to choose which room to go: morphine-dependent mice always choose the room in which they were planted right after the substance was introduced.

The brain activity of mice was studied using calcium imaging: in paraventricular nucleus of the thalamus, the mice were administered AAV virus expressing the indicator, which binds with calcium ions in the occurrence of the neuronal action potential. Other terminals in other areas — the amygdala and the nucleus accumbens, the mice implanted with an optical fiber. Thus, the researchers photometrically measured the appearance of calcium ions (and thus neuronal activity) in both the paraventricular nucleus and neural paths from it to other sites.

Scientists have found that the activity of the path between the paraventricular nucleus of the thalamus and the Central nucleus of the amygdala is necessary for the formation of a connection between a particular room and the fact that it the mouse can get morphine. Mice that inhibited the way artificial drugs, introducing pre-DREADD receptors, significantly (p < 0.001) less frequently showed interest in morfinova the room during training (that is, when they tried to “plant” on the matter). Interestingly, this effect persisted the next day, when the activity path is not limited.

Activation of this path optogenetics — through the introduction of kanalstein-2 excited by a laser with a wavelength of approximately 470 nanometers — has not led to the fact that mouse began to actively look for the passage to morfinova room. This means that the connection between the paraventricular nucleus and amygdala not associated with seeking compensation as such, but just helps to associate environmental factors with the material, forming the Association.

As for the way between the paraventricular nucleus of the thalamus and adjacent the core, his DREADD-inhibition led to the fact that the mouse ceased to associate a particular room getting morphine: mice showed significantly (p < 0.001) less interest in morfinova room in a day and ten days after the inhibition of the way. Scientists have concluded that this path is responsible for storing the memories of the already formed connection between the room and the fact that it is possible to obtain a morphine that, in fact, prevent relapse.

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