- The anti-depressant Prozac causes a dramatic increase
in aggressive behaviour in mice the day after the drug is administered,
US researchers have found.
Prozac, or fluoxetine, has been associated with isolated reports of suicide
and crimes of violence in people. "But this has been difficult to
study in other animals," says George Wagner of Rutgers University.
"Our findings represent the first demonstration that the drug can
actually increase defensive aggression in other species."
When the mice received alcohol along with Prozac, their aggression scores
on the following day were even higher. "Our data indicate a potentially
serious interaction between Prozac and alcohol," Wagner adds.
However, the implications for the millions of people who take Prozac worldwide
are unclear, Wagner says. The mice in his study were given a single, very
high dose of the drug. The effects of regular, much smaller doses over
a long period of time might be different, he says.
John Mann of Columbia University, US, says: "This is a very interesting
observation. But individual case reports of people exhibiting suicidal
or aggressive behaviour have been found with practically every psychotropic
medication. Every double blind study of people taking Prozac to date has
not indicated an association with increased aggression."
- Protruding object
- Mann's team investigated the effects of Prozac alone,
alcohol alone, and Prozac plus alcohol on two types of aggression: offensive
"Offensive would be two males fighting over territory, for example,"
says Mann. "Defensive involves an aggressive response to a painful
or frustrating stimuli."
Mice in the three drug groups were put in a cage together, to investigate
offensive aggression, or given a mild electric shock, to investigate defensive
aggression. In the second case, the mice's tendency to bite an inanimate
object protruding into their cage in response to the shock was measured.
Prozac is thought to work by prolonging the presence of the neurotransmitter
serotonin in the brain. Low levels of serotonin are associated both with
alcohol consumption and with aggression. The team expected that alcohol
alone would boost aggression - and that this effect would be counteracted
by an accompanying dose of Prozac. Prozac alone was expected to decrease
On the day the drugs were given, that was exactly what they found. But
on the second day, they found that defensive aggressive behaviour in mice
that had received Prozac alone rocketed by between 15 and 20 per cent,
compared with baseline measurements. In mice that had also received alcohol,
it increased by between 20 and 25 per cent. There was no effect on offensive
- Impulsive behaviour
- Because Prozac works by prolonging the presence of serotonin
- rather than boosting release of the neurotransmitter - it causes a decrease
in levels of a serotonin metabolite called 5-hydroxyindoleacetic acid (5HIAA).
Low levels of 5HIAA have been associated with suicides, especially violent
ones, as well as with other violent or impulsive behaviour.
Wagner's team recorded the lowest levels of 5HIAA on the day after the
mice received the Prozac.
"We found lower levels of 5HIAA in our mice long after they received
fluoxetine," says Wagner. "That may help explain their increased
The team now plans to investigate the effects of chronic Prozac use on
aggression in animals.
Wagner presented his research at the Society for Neuroscience annual conference
in San Diego.