• Goddard, Andrew (PI)

Project: Research project

Project Details


There considerable preclinical data demonstrating an important role for
the brain noradrenergic (NE) and serotonergic (5-HT) neurotransmitter
systems in the expression of fear in animals. These systems also
appear to be involved in the pathophysiology of human anxiety, since
panic disorder (PD) patients have a marked behavioral (anxiety),
physiologic and biochemical response to the alpha 2 adrenergic
antagonist yohimbine implicating NE dysregulation in PD, and panic
patients improve clinically following chronic administration of
medications which influence 5-HT function, like the serotonin reuptake
inhibitors. There is a large amount of data describing the intimate
anatomic and functional relationships between the NE and 5-HT systems
in laboratory animals, but there is little data on the interaction of
these two systems in humans. We have recently demonstrated an increase in the anxiogenic effects of
yohimbine in healthy human subjects who have ingested an amino acid
drink that depletes plasma tryptophan by over 80%. This suggests that
an acute impairment of 5-HT function increases the symptomatic response
to increased NE activity. We will test the hypothesis that rapid reduction of brain serotonin
levels will markedly increase the symptomatic response to the alpha 2
adrenergic antagonist, yohimbine, in PD patients. In order to evaluate
this prediction we propose first to study the behavioral effects of
tryptophan (TRP) depletion alone in a group of PD patients, since the
effects of TRP depletion have not been systematically evaluated in
these patients. Then we will examine the behavioral response of a
separate group of PD patients to a combined challenge with TRP
depletion followed by intravenous yohimbine 0.2 mg/kg. If there is not
a marked change in symptomatic response to this dose of yohimbine, we
will repeat the combined challenge using a dose of 0.3 mg/kg yohimbine.
The knowledge acquired could contribute to a deeper understanding of
the pathophysiology of PD and the therapeutic mechanisms of action of
successful antipanic treatments.
Effective start/end date4/1/933/31/95


  • National Institutes of Health: $70,815.00
  • National Institutes of Health


  • Medicine(all)


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