A drug of the Tac2 neuronal circuit, involved in the formation of the memory of fear, has opposite effects on the ability to remember aversive events in mice according to sex: it is reduced in male mice and increased in female mice.
This is the first time that a drug has been shown to produce this opposite effect on the memory of male and female mice. The study also evidences that opposing molecular mechanisms and behaviours can occur in memory formation depending on sex. The study has been published in Nature Communications.
The research group on Translational Mechanisms of Fear Memory, led by Raül Andero, has been studying the functioning of fear memory for years to find treatments for pathologies associated with traumatic experiences, such as post-traumatic stress and phobias.
The research team had identified that the Tac2 circuit, located in the amygdala, could be temporarily blocked by the effect of a drug they are studying. This drug, called Osanetant, was able to reduce the capacity to recall traumatic events in male mice. In the study, they discovered that this same drug produces the opposite effect in female mice, increasing their fear memory.
This opposite effect is explained by the fact that, in blocking the Tac2 pathway, the drug interacts with the neuronal receptors of two sex hormones: testosterone in males and estrogen in females. In addition, it has been observed that hormonal fluctuations during the oestrous cycle in female mice, equivalent to the menstrual cycle in women, vary the effects of the drug on the ability to remember aversive events.
In the field of neurosciences, only one study in females is published for every 5.5 done in males. And research on Tac2 pathway has also been done mostly in males so far.
The drug studied is not new, but it is safe for use in humans. However, at the moment it is not being used to treat any disease. Prof. Andero’s group is now investigating its potential use in treating fear disorders differently by sex.
