Thread by @DrEricDing

🧠New study shows a drug that affects neurons that form fearful memories, has opposite effects on remembering events by sex—it *reduces* the capacity to recall traumatic events in male mice, but opposite effect in female mice of *increasing* fear memory.😮
scitechdaily.com/same-drug-can-…

2) “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 behaviors can occur in memory formation depending on sex.”

3) “The research group on Translational mechanisms of the memory of fear 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.”

4) 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 is called Osanetant.

5) “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.”

6) “ In addition, it has been observed that hormonal fluctuations during the estrous cycle in female mice, equivalent to the menstrual cycle in women, vary the effects of the drug on the ability to remember aversive events.

7) ”These results demonstrate the ability that hormones have to modulate the formation of fear memories, and show the need to consider sex differences and hormonal cycles in the design of pharmacological treatments for psychiatric disorders”, says Antonio Florido, first author.

8) “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.”

9) I know a few things about both sex differences due to sex hormones - we see opposite effects for testosterone and diabetes too. One of my old Harvard thesis papers. jamanetwork.com/journals/jama/…

10) in the study (among several others we published), testosterone lowered diabetes risk in men, but increased diabetes and glucose in women. Many trials have found this too.

11) hence getting both men and women to do studies is critical. as for women and men in willingness to participate in clinical trials, my other long-ago paper found a clear gap in willingness, due to perceived risks and benefits. pubmed.ncbi.nlm.nih.gov/17502531/