The recent Congressional hearings on anabolic steroid abuse by professional athletes helped to shed light on the dangers of performance-enhancing drugs. And ongoing research at Dartmouth is helping to illuminate how prolonged use of steroids may trigger irreversible molecular changes in the brain, especially in adolescent females.

Abuse: Anabolic-androgenic steroids (AAS), synthetic derivatives of testosterone, are controlled substances used by some athletes to build muscle and increase body size. "These are increasingly used drugs of abuse," says Leslie Henderson, Ph.D., a professor of physiology and of biochemistry at DMS. "In particular, the use among junior high and high school kids has been escalating." The Centers for Disease Control and Prevention reported in 2001 that 5% of all high schoolers had used steroids without a prescription.

"The most common side effects associated with chronic steroid abuse," Henderson says, "are changes in aggression, anxiety, and sexual behaviors." These changes have been known for some time, but there has "not been a lot done to try and understand the underlying basis" for them.

Henderson, in collaboration with Ann

Photo by Jon Gilbert Fox

Henderson studies steroids' basic mechanisms.

Clark, Ph.D., a professor of psychological and brain sciences at Dartmouth College, has reported that AAS use affects behavior and interferes with the expression of signaling molecules in the brain. Henderson's lab looks at how these steroids affect a neurotransmitter receptor, the gammaaminobutyric acid type A (GABAA) receptor. The GABAA receptor, an ion channel in the brain, allows negatively charged chloride ions to flow rapidly into neurons. The inward flow of chloride ions inhibits nerve-cell activity by preventing the generation of electrical signals that travel along neurons.

In the short term, AAS use exploits this

natural process by allowing GABAA receptors to remain open longer. The increased chloride ion flow dampens activity in the central nervous system and may contribute to the antianxiety effect that is reported with initial AAS use.

But long-term AAS use can produce very different effects, including increased anxiety or aggression. In mice, chronic steroid exposure alters the expression of some GABAA receptor subunit genes. One kind of steroid decreased expression of these genes in areas of the brain important in reproduction and aggression in female but not male mice; it also had more effect on adolescents than adults.

Awareness: Henderson and Clark hope their work will heighten public awareness of the risks of AAS use among adolescents, girls in particular. They also hope a better understanding of the underlying mechanisms may lead to new therapies. For example, DMS's Hillary White, Ph.D., has shown that androgens may ameliorate symptoms of fibromyalgia.

Henderson says their own work is far from the clinical stage, but that "overall understanding of how these drugs affect transmission in the brain could have broad repercussions."

Sion E. Rogers