BioEd Online

Children or unborn babies exposed to the popular antidepressant Prozac could suffer from abnormal emotional development, animal studies suggest.

Rats given the drug for the first few weeks of life perform poorly on tasks designed to test their confidence and ability to deal with stress, says psychiatrist Jay Gingrich, who ran the study with his colleagues at Columbia University in New York.

The group says its findings should be taken into consideration when prescribing Prozac (also known as fluoxetine) and related antidepressants to pregnant mothers and young children. But it adds that it is too early to consider banning use of the drugs in those patients.

Gingrich's colleague Mark Ansorge assessed the rats' behaviour by placing them in a cross-shaped maze raised above the floor, a test that measures the willingness of the animals to explore an unusual environment. Adult rats dosed with Prozac early in life were less interested in venturing far from their starting point and spent less time moving around. Animal researchers take this behaviour as evidence of abnormal emotional development.

Related tests revealed that rats given Prozac are also less willing to take risks to earn rewards such as food and take longer to escape unpleasant environments, a sign that they deal poorly with stress. The results were revealed on 26 October at the annual meeting of the Society for Neuroscience, held in San Diego, California. They will be published in the journal Science this week¹.

Balancing act

Gingrich says it is vital that work is now done to assess whether these effects are relevant to humans. Making connections between species is difficult, but he notes that the rats were given a dose comparable to that which humans receive.

Gingrich adds that the animals received the drugs a few days after birth, the stage of their development equivalent to the final third of a human pregnancy.

But psychiatrists also warn that Prozac and related drugs prove very helpful to pregnant women. "Many pregnant women demand this treatment," says Paul Plotsky, a neuroscientist at Emory University in Atlanta, Georgia. "They may otherwise have suicidal thoughts or a desire to kill their infants after birth."

"Every time I prescribe there is a risk," agrees Gingrich. "I won't be changing my recommendation based on these results, but this underscores the need for research on human subjects."

Changing cells

Exactly why Prozac affect the rats' behaviour is not known, but it may be due to the impact of the drug on receptors for serotonin, a chemical found in the brain that influences mood and emotion.

Prozac works by preventing serotonin from being recycled by brain cells and is one of a recently developed family of drugs known as selective serotonin reuptake inhibitors. Gingrich believes this may influence the way that serotonin-producing cells change as the rats' brains develop.

The theory is backed up by studies of rats that have been genetically engineered to lack the molecules that recycle serotonin. These rats have fewer serotonin-producing cells in the brainstem, an area that controls basic functions such as breathing and that connects widely to other areas of the brain. The serotonin cells that remain also fire less frequently than normal, adds Gingrich. Such rats exhibit behaviour similar to those in Gingrich's study.