Football commentator John Madden fears flying. Acclaimed singer
Barbara Streisand fears public appearances. Ironically, even the
head of the Center for Behavioral Neurosciences Fear Collabora-tory
once was afraid of speaking in public.
I eventually overcame my fear, but a lot of people never
do, said Michael Davis, Wood-ruff Professor of Psychiatry
and Behavioral Science. For some, excessive fear can be paralyzing
As a behavioral neuroscientist, Davis has spent almost two decades
puzzling out the brain systems and circuitry involved in fear. With
this knowledge, one of his goals has been to develop a therapeutic
adjunct to psychotherapy for people suffering from a range of disorders
associated with the fear response.
Davis and his colleagues recently discovered what could be a significant
breakthrough. Administering a drug called D-cycloserine (DCS), which
has been used for years to treat tuberculosis, Davis successfully
suppressed the fear response in rats that had been conditioned to
associate the appearance of lights with an electric shock. DCS did
not promote fear extinction in the absence of lights; instead, Davis
found it had to be administered at the same time the lightsthe
Rats provide ideal models for understanding the fear response.
Using classic fear conditioning, Davis teaches the rats to associate
the appearance of a light with an electric shock. He can confirm
that the animals are afraid because they are more easily startled
by a loud sound when the light is on. By the same conditioning,
he can extinguish their fear response after repeated episodes when
the glow of the lights does not result in an electric shock.
In the early 1990s, Davis conducted two studies that revealed the
central role of an area of the brain called the amygdala and the
glutamate receptor N-methyl-D-aspartate (NMDA) in regulating the
fear response. In the first experiment, Davis found that a drug
that blocks the activity of the neurotransmitter glutamate at this
NMDA receptor suppressed the rats ability to learn to fear
the lights. A second study demonstrated that a similar NMDA antagonist
prevented fear extinction. Despite the fact that an electric shock
did not accompany the lights during multiple presentations, the
rats continued to jump in anticipation of the shock.
Biochemical processes are clearly involved in the fear response,
which can be quantitatively assessed by changes in heart rate, blood
pressure, perspiration and the release of certain hormones. However
Davis said that, in fact, most fears are learned.
Fear memories probably never go away, Davis said. Instead,
most people learn to deal with them or suppress them. DCS, when
administered simultaneously with the presentation of the fear stimulus,
basically promotes a new form of learning to cope with memories
of an aversive event.
Given that DCS is already FDA approved, Davis (and a research team
that includes Fear Collaboratory members Kerry Ressler and Barbara
Rothbaum) is planning a clinical trial to assess the drugs
ability to promote fear extinction in people suffering from a variety
of phobias, anxiety, panic and post-traumatic stress disorders.
The study will draw on Resslers and Rothbaums clinical
experience in treating post-traumatic stress disorders and Rothbaums
ability to create virtual-reality simulations of fear-inducing events.
For someone with an excessive fear of heights, Rothbaum has simulated
a self-controlled glass elevator going up the outside of a 50-story
building. Acrophobics initially can only rise to the second or third
floor, but after several sessions, their fear begins to wane and
they can go to higher floors.
DCS should speed up this process, Davis said. Virtual-reality
technology provides a well-controlled psychotherapeutic situation
to see if DCS will improve the outcome of treating acrophobics and,
hopefully, people suffering from more complex anxiety conditions,
such as panic and post-traumatic stress disorders.
While cautious about whether DCS can permanently extinguish a debilitating
fear disorder, Davis sees much opportunity to explore the drugs
ability to treat a variety of psychological disorders, even drug
The same sort of learned responses associated with fear are
involved with drug craving, Davis said. The sight of
drug paraphernalia or a street corner where the drugs were purchased
are powerful cues that produce craving. DCS, in combination with
psychotherapy, could be used to extinguish these connections and
ultimately learn a new way to cope with craving.
Davis study appeared this spring in The Journal of Neuroscience.
His co-authors include David Walker, Ressler and Kwok-Tung Lu in
psychiatry and behavioral sciences. The research is supported by
the CBN and grants from the National Institute of Mental Health.