Scientists identify new pathway of antidepressant action

Scientists at UC San Francisco have discovered a new chemical pathway in the brain by which the most common antidepressants may alter mood. The research demonstrates that many popular mood modulators trigger chemical activity along more than one track at a time. It shows too how a brain chemical, known as a neurosteroid, might make a prime target for drugs to improve severe mood swings.

The researchers are publishing their study in the November 9 issue of the Proceedings of the National Academy of Sciences (PNAS).

Antidepressants such as Prozac, Paxil and Zoloft are thought to relieve depression by increasing the availability of one of the body's natural mood-enhancing chemicals, the neurotransmitter serotonin. But the UCSF experimenters examined the effect of these same antidepressants on an entirely different chemical pathway -- one increasingly thought to play a role in mood regulation as well. It involves a natural brain compound called a neurosteroid, only recognized in the last 10 or 15 years.

The scientists discovered that all three of these antidepressants, known as SSRI's, not only affect serotonin availability, but also greatly increase the synthesis of a key neurosteroid -- 10 to 30-fold. The profound effect, they found, comes from the SSRI's ability to greatly boost the action of the final enzyme involved in the synthesis of the neurosteroid in the brain.

"Each of these three serotonin reuptake inhibitors, or SSRI's, shows a dramatic positive effect on the levels of allopregnanolone, a steroid made in the brain, which most likely modulates mood and plays a role in heightened anxiety and depression found in severe premenstrual disorders and other conditions," said Synthia Mellon, PhD, senior author on the PNAS study and a professor of reproductive endocrinology at UCSF.

"The study points to the likelihood that SSRI's control mood by more than the one pathway that has received most of our attention, and it suggests that the ster

Contact: Wallace Ravven
University of California - San Francisco

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