Acne drug leads to depression-related behavior in mice

Sep 21 2006

A drug commonly used to treat severe acne can lead to depression-related behavior in mice, according to research published in the journal Neuropsychopharmacology by scientists from The University of Texas at Austin and the University of Bath.

The scientists gave 13-cis-retinoic acid, the active ingredient in Accutane, to mice over six weeks and monitored their behavior.

They found these animals spent significantly more time motionless in a range of behavioral tests compared to untreated animals. Experiments were designed to test the natural escape-related behaviors of the mice in mildly stressful situations.

Mice treated with 13-cis-retinoic acid showed less escape-related behavior than control mice, an indication of depression in these animals.

Since Accutane's introduction in the early 1980s there have been controversial reports of depression and suicidal behavior that may have occurred in some people taking the drug. However, the biological mechanism by which this might happen has never been established.

"Human studies concerning Accutane and depression have generated conflicting results," said Dr. Michelle Lane, corresponding author and assistant professor of human ecology at The University of Texas at Austin. "Humans have self-image and social stresses which can contribute to the development of depression. Mice lack these confounding variables, allowing us to examine the effect of the drug itself on behavior."

"Without more research it is difficult to say for sure whether the same link applies to people taking the drug," said Dr. Sarah Bailey, co-author from the Department of Pharmacy and Pharmacology at the University of Bath. "This laboratory evidence provides a useful model for future research into Accutane and understanding how this family of compounds affects the brain."

Accutane belongs to a group of chemicals called retinoids. This group includes vitamin A and vitamin A-related compounds known to affect development of the nervous system. For this reason Accutane is not prescribed to pregnant women.

"Retinoids have long been studied for their ability to affect the development of the nervous system," said Lane, a nutritional scientist whose research focuses on retinoids. "However, new evidence suggests that retinoids can alter the function of the adult brain. For example, there is some evidence that high dietary vitamin A may cause psychiatric symptoms such as hysteria."

This research is the first to demonstrate that retinoids are capable of influencing depression-related behaviors.

It is not known how Accutane affects the brain, but Lane and Bailey hope to explore this phenomenon further in the future.