Pigs cured of depression

Psilocybin increased the number of interneuronal connections in pigs

Anna Muravyeva, N+1

A single injection of psilocybin increased the number of synapses in the brain of pigs and reduced the number of 5-HT _2A serotonin receptors, according to a study published in the International Journal of Molecular Sciences. An autoradiographic study of the brain showed such results for the hippocampus and prefrontal cortex of animals, which are associated with the generation of emotions. This result may be related to the antidepressant effect of psilocybin.

Clinical studies show that psilocybin has a therapeutic effect in depressive and anxiety disorders. Even a single dose of psilocybin can significantly reduce anxiety in patients. Perhaps this is due to its effect on 5-HT _2A serotonin receptors: the molecule is similar to the serotonin molecule and is able to activate its receptors.

At the same time, patients with depression have a decrease in the number of interneuronal contacts (synapses) in the areas of the brain associated with emotions: the hippocampus and prefrontal cortex. This occurs as a result of the suppression of the activity of synaptic proteins and genes in these areas, therefore, for a long-term therapeutic effect, it is necessary not only to replace serotonin, but also to restore their work and increase the number of synapses. 

Researchers from the University of Copenhagen led by Nakul Raval (Nakul Ravi Raval) suggested that the therapeutic effect of psilocybin may be associated with the restoration of the number of synapses in the hippocampus and prefrontal cortex. To understand whether this substance has such properties, biologists once injected a hallucinogenic dose of psilocybin into 24 pigs, and then after one and seven days studied their brains.

To count the number of synapses, the scientists used autoradiography: they processed the brains of pigs with radioactive ligands that selectively bound to the synaptic protein SV2A and caused it to emit. The number of synapses was judged by the radiation from SV2A. In the same way, the number of 5-HT2A serotonin receptors was calculated: It has been shown that after their activation, the cell "hides" receptors from the membrane into cytoplasmic vesicles, where they can be digested and split. That is, a decrease in the number of receptors may correspond to their recent activation.

The amount of SV2A protein (and, as a consequence, synapses) in the hippocampus turned out to be greater than in the control group, both the next day and a week after psilocybin injection (p<0.05). In the prefrontal cortex, only the difference was significant on the seventh day after injection (p<0.0001). In both departments, the number of 5-HT2A receptors decreased, but only on the first day (p<0.05). At the same time, the number of functionally active receptors decreased more.

These results confirm that psilocybin is involved in neuroplasticity and promotes the formation of synapses after activation of serotonin receptors. Now biologists have to figure out which proteins are involved in this process in order to understand the antidepressant properties of hallucinogens.

A similar study was recently conducted on smaller animals – rats. In it, biologists investigated not the number of connections, but the activity of genes associated with neuroplasticity and the formation of new synapses in the prefrontal cortex, and came to similar conclusions.

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