Researchers are attempting to define the mechanism by which testosterone, the primary male sex hormone, serves as an antidepressant.
Although gains have been made, the exact mechanisms underlying its effects have remained unclear. Graduate student Nicole Carrier and neuroscientist Mohamed Kabbaj, Ph.D., of Florida State University are actively working to elucidate these mechanisms.
They’ve discovered that a specific pathway in the hippocampus, a brain region involved in memory formation and regulation of stress responses, plays a major role in mediating testosterone’s effects.
Their findings are presented in the journal Biological Psychiatry.
Health professionals have observed that compared to men, women are twice as likely to suffer from an affective disorder like depression.
Furthermore, men with hypogonadism, a condition where the body produces no or low testosterone, also suffer increased levels of depression and anxiety. Clinically, testosterone replacement therapy has been shown to effectively improve mood.
While the outcomes of the interventions are known, it is important to fully characterize how and where these effects are occurring. Investigators believe this knowledge will to better target the development of future antidepressant therapies.
In the current experiment, scientists performed multiple experiments in neutered adult male rats. The rats developed depressive-like behaviors that were reversed with testosterone replacement.
They also “identified a molecular pathway called MAPK/ERK2 (mitogen activated protein kinase/ extracellular regulated kinase 2) in the hippocampus that plays a major role in mediating the protective effects of testosterone,” said Kabbaj.
This suggests that the proper functioning of ERK2 is necessary before the antidepressant effects of testosterone can occur. It also suggests that this pathway may be a promising target for antidepressant therapies.
Researchers observed that the testosterone replacement medicine appeared to have less of an affect than the administration of common antidepressants.
Kabbaj comments, “Interestingly, the beneficial effects of testosterone were not associated with changes in neurogenesis (generation of new neurons) in the hippocampus as it is the case with other classical antidepressants like imipramine (Tofranil) and fluoxetine (Prozac).”
In results published elsewhere by the same group, testosterone has shown beneficial effects only in male rats, not in female rats.