Baby rats given Prozac show skewed emotions later in life.
by Jim Giles

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 week 1.

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.

See also:
http://www.nature.com/news/2004/041025/full/041025-14.html
http://www.sciencemag.org/cgi/content/abstract/306/5697/879?view=abstract