Rat Brain’s Executive Hub Quells Alarm Center if Stress is Controllable
Treatments for mood and anxiety disorders are thought to work,
in part, by helping patients control the stresses in their lives.
A new study in rats by National Institutes of Health (NIH) grantees
provides insight into the brain mechanisms likely involved. When
it deems a stressor controllable, an executive hub in the front
of the brain quells an alarm center deep in the brainstem, preventing
the adverse behavioral and physiological effects of uncontrollable
stress.
"It’s as if the prefrontal cortex says: ‘Cool
it, brainstem! We have control over this and there is no need to
get so excited'," quipped Steven Maier, Ph.D., University
of Colorado, whose study was funded by the National Institute of
Mental Health (NIMH) and the National Institute on Drug Abuse (NIDA).
Maier and colleagues posted their findings online in Nature
Neuroscience,
February 6, 2005.
Lack of control over stressful life experiences has been implicated
in mood and anxiety disorders. Rats exposed to uncontrollable stress
develop learned helplessness, a syndrome similar to depression
and post traumatic stress disorder (PTSD). They lose the ability
to learn how to escape stressors. Activation of a brainstem area
(dorsal raphe nucleus) has been implicated in such reactions. But
this area is too small and lacks the proper sensory inputs to judge
whether a stressor is controllable. Many of its inputs come conspicuously
from the mid-prefrontal cortex area (medial prefrontal cortex),
seat of higher order functions, such as problem-solving and learning
from experience. These signals are sent via the chemical messenger
serotonin, which is involved in mood regulation and in mediating
the effects of the most widely prescribed antidepressants. The
medial prefrontal cortex has also been implicated as the source
of an “all clear” signal that quells fear in rats.*
To find out the role of the medial prefrontal cortex, Maier’s
team chemically inactivated it in rats that were learning to control
a stressor. The animals showed the same brainstem activation and,
eventually, the same behaviors characteristic of depression (failure
to learn to escape) and anxiety (exaggerated fear conditioning)
as rats exposed to uncontrollable stress.
“If an organism can cope behaviorally with an event, there’s
no need for intense physiological adaptation. It has been assumed
that when stressors are uncontrollable the organism learns this,
and that it is this uncontrollability that sets off the neural
cascade,” explained Maier. “However, our data suggest
that instead it is control that is the active ingredient. If the
organism has control and can cope behaviorally, this is detected
by the cortex, which then sends inhibitory signals to the brainstem.”
In PTSD, which is triggered by uncontrollable stress, medial prefrontal
cortex activity is reduced. Proposing an analogous mechanism, Maier
speculated that loss of inhibition from the medial prefrontal cortex
may explain increased activity of the amygdala (a fear hub) in
PTSD.
Also participating the study were: Drs. Jose Amat, Erin Paul,
Sondra Bland, Linda Watkins, and Michael Baratta.
NIMH and NIDA are part of the National Institutes of Health
(NIH), the Federal Government's primary agency for biomedical
and behavioral research. NIH is a component of the U.S. Department
of Health and Human Services.
*See news release: Mimicking
Brain’s ‘All Clear” Quells
Fear in Rats <http://www.nimh.nih.gov/Press/prsafetysignal.cfm> Amat J, Baratta MV, Paul E, Bland ST, Watkins LR, Maier SF. Medial
prefrontal cortex determines how stressor controllability affects
behavior and dorsal raphe nucleus. Nat Neurosci. 2005 Feb 06; [Epub
ahead of print].
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