Differences in brain chemistry between adolescents and adults may explain why some teenagers given a selective serotonin reuptake inhibitor become aggressive or suicidal, according to an article in the October issue of Behavioral Neuroscience.

Neuroscientists at the University of Texas at Austin found that juvenile hamsters given low doses of fluoxetine hydrochloride became more aggressive on low doses. Juveniles given high doses became somewhat less aggressive, but not as much as adult hamsters, who calmed on both high and low doses.

Doctoral student and lead author Kereshmeh Taravosh-Lahn, BA, said the findings confirm that juvenile and adult brains are different and “It is unwise to expect a drug to work the same in juveniles as in adults.”

Fluoxetine is the only medication approved in the USA to treat depression in children and adolescents. However, it has carried a “black box” warning since Fall 2004 due to findings of increased risk of suicidal thoughts and behaviors in some child and adolescent patients.

Fluoxetine is known to inhibit aggression in adult hamsters. Hamsters are often used as an animal model for studying the neural basis of social behavior, given how the rodents’ youthful play fighting develops in clearly understood stages into adult aggression.

In the study, researchers injected each hamster with high or low doses of fluoxetine. Two hours later, they put a smaller, younger same-sex hamster into the experimental hamster’s home cage for 10 minutes, creating a threatening situation to which male hamsters usually respond with aggression. The neuroscientists videotaped the encounters to document behaviors such as attacks, pins, contact time, contact bouts, and target of attack.

Adult hamsters treated with either dose of fluoxetine became generally more peaceful, attacking less often and for shorter times. However, the juveniles responded differently, both to high and low doses. The low doses actually resulted in significantly longer, more frequent and intense attacks, whereas the high dose only partly inhibited aggression. Neither set of juveniles responded as well as adults; low-dose hamsters actually did worse.

Thus, although fluoxetine consistently calmed adults in a potentially threatening situation, it differentially affected the juveniles. The effects of fluoxetine on aggressive responses appeared to be specific to both age and dose.

The neuroscientists explained that because adolescents may have lower levels of serotonin than adults, there may not be enough for the selective serotonin reuptake inhibitor to work effectively. In addition, researchers are investigating whether changing ratios of different subtypes of serotonin receptors ? some of which inhibit and some of which enhance aggression -- are implicated in the findings of higher aggression on low doses.