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Animal models show that anabolic steroids flip the adolescent brain's switch for aggression

February 27, 2006

Hamsters with 'roid rage' reveal that human teens may stay nasty for more than two years, with possible long-term brain impact

Anabolic steroids not only make teens more aggressive, but may keep them that way into young adulthood. The effect ultimately wears off but there may be other, lasting consequences for the developing brain. These findings, published in February's Behavioral Neuroscience, also showed that aggression rose and fell in synch with neurotransmitter levels in the brain's aggression control region. Behavioral Neuroscience is published by the American Psychological Association (APA).

Neuroscientists are deeply concerned about rising adolescent abuse of anabolic-androgenic steroids (AASs), given the National Institute on Drug Abuse's estimate that nearly half a million eighth- and 10th-grade students abuse AASs each year. Not only do steroids set kids up for heavier use of steroids and other drugs later in life, but long-term users can suffer from mood swings, hallucinations and paranoia; liver damage; high blood pressure; as well as increased risk of heart disease, stroke and some types of cancer. Withdrawal often brings depression, and recent research suggests that some AASs may even be habit-forming.

Overseen by Richard Melloni Jr., PhD, of Northeastern University in Boston, the current study of 76 adolescent hamsters compared how individual hamsters behaved when another hamster was put into their cages. Normally mild-mannered hamsters still defend their turf, learning aggression during puberty by play-fighting, much like humans. Their roughhousing normally includes wrestling and nibbling - pretty tame stuff.

However, hamsters injected with commonly used steroids (suspended in oil) became extremely aggressive. Even after the drug was withdrawn, the newly vicious hamsters attacked, bit and chased the intruders. In fact, their aggressiveness measured ten times greater than that of control hamsters injected with oil only. Their full-blown aggression - clearly drug-induced - lasted for nearly two weeks of withdrawal, the equivalent of half their adolescence. Eventually, the aggressiveness subsided; by three weeks of withdrawal, all the hamsters greeted intruders with normal, playful defensiveness.

Autopsy revealed that the outward aggressiveness correlated with inner changes in the brain. When the drugged hamsters were hostile hosts, a part of their brains called the anterior hypothalamus pumped out more of a neurotransmitter called vasopressin. By three weeks of withdrawal, vasopressin levels subsided in parallel with the aggressive behavior. The anterior hypothalamus regulates aggression and social behavior. Thus, vasopressin - already known to stimulate that area - appears to fuel the engine of aggression. And, says Melloni, "Steroids step on the gas for agression."

Thus, the neuroscientists conclude that the aggressiveness triggered by anabolic steroids, although reversible, may last long enough to create serious behavioral problems for adults. Because this part of the rodent and human nervous systems are similar, researchers generalize their findings to humans. As a result, Melloni and his colleagues speculate that anabolic steroids can dramatically shorten teenage fuses (not known for length under the best of circumstances) and make young people "pop off" for years, a danger to themselves and to others. Melloni and others researchers also are concerned that drug use during a critical window in brain development can change their wiring for good. He says, "Because the developing brain is more adaptable and pliable, steroids could change the trajectory if administered during development." His lab is releasing other new findings, as yet unpublished, that the serotonin system - implicated in depression - may never recover.

"If you hit the right areas of the brain at the right time, you make permanent changes," Melloni concludes from the converging evidence.

He hopes that adolescents don't take the ultimate recovery of the vasopressin system to mean it's OK to use the drugs. "It's our hope that people considering the use of these drugs weigh the long-term health risks and the serious potential for aggression and violence. Muscle mass and medals aren't worth the risk of hurting someone or landing in jail."

Finally, researchers such as Melloni hope these new insights can lead to treatments for aggressive behavior, with or without steroid abuse. "Linking aggression to fluctuations in vasopressin makes it an important neurotransmitter to target for pharmacotherapy," he says.

American Psychological Association