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| Sponsor: | National Institute of Mental Health (NIMH) |
|---|---|
| Information provided by: | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier: | NCT00109642 |
Purpose
This study will examine the role of a brain chemical called norepinephrine in thinking, decision-making, and emotional processing. After norepinephrine is released from a brain cell, it binds to another brain cell's receptor. Some of the receptors it binds to are called alpha-2 adrenergic receptors. This study will use medicines called yohimbine and guanfacine to look at the function of norepinephrine in the brain when it binds to the alpha-2 adrenergic receptors. Yohimbine increases norepinephrine's function and guanfacine decreases its function.
Healthy volunteers between 20 and 50 years of age who do not have heart disease, high blood pressure, psychiatric illness, or other serious medical conditions and who are not allergic to lactose may be eligible for this study. Candidates are screened with a medical and psychiatric history, physical examination, neuropsychological testing, blood and urine tests and electrocardiogram. Women are screened with a urine pregnancy test.
Participants are given a pill of yohimbine, guanfacine, or placebo and undergo the following tests and procedures:
| Condition |
|---|
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Psychopathy Mental Disorders |
| Study Type: | Observational |
| Official Title: | Investigating the Role of Norepinephrine in Emotional Processing Through Alpha-2 Adrenergic Receptor Modulation |
| Estimated Enrollment: | 216 |
| Study Start Date: | April 2005 |
| Study Completion Date: | March 2009 |
| Primary Completion Date: | March 2009 (Final data collection date for primary outcome measure) |
An understanding of the role of specific neurotransmitters in the neurocognitive functions mediating emotional processing is essential for the understanding and treatment of mood and anxiety disorders. One such disorder, currently regarded as untreatable, is psychopathy. Psychopathy has been linked with noradrenergic and amygdala disturbances. However, an understanding of the functional significance of the noradrenergic system in humans remains in its infancy. The goal of this protocol is to use targeted noradrenergic manipulations (yohimbine and guanfacine) in conjunction with specific neurocognitive and neuroimaging paradigms to consider the role of norepinephrine in reward and punishment processing. In particular, we wish to evaluate the hypothesis that increased norepinephrine levels following the administration of yohimbine will lead to enhanced formation and processing of stimulus-reward and stimulus-punishment associations, while decreased norepinephrine levels following the administration of guanfacine will reduce the formation and processing of stimulus-reward and stimulus-punishment associations. In addition, we aim to examine the hypothesis that increased norepinephrine levels will lead to increased neural response in the amygdala during either the formation, or processing, of stimulus-reinforcement associations.
Eligibility| Ages Eligible for Study: | 20 Years to 50 Years |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | Yes |
Age: Participants will be males and females, 20-50 years of age.
IQ: IQ, as measured by 4 subscales from the Wechsler Adult Intelligence Scale-Revised (WAIS-R), must be greater than 80.
Medication status: No current use of any psychotropic medication or benzodiazepine.
EXCLUSION CRITERIA:
Because factors such as psychiatric disease, or CNS disease, can influence functional brain activity, these factors are exclusionary:
Additional exclusion criteria for fMRI studies:
Contacts and Locations
More Information
| Study ID Numbers: | 050147, 05-M-0147 |
| Study First Received: | April 29, 2005 |
| Last Updated: | August 27, 2009 |
| ClinicalTrials.gov Identifier: | NCT00109642 History of Changes |
| Health Authority: | United States: Federal Government |
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Amygdala Orbitofrontal Cortex Yohimbine Emotion |
Guanfacine Norepinephrine Healthy Volunteer |
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Neurotransmitter Agents Adrenergic alpha-Agonists Adrenergic Agents Molecular Mechanisms of Pharmacological Action Sympathomimetics Physiological Effects of Drugs Cardiovascular Agents Adrenergic Agonists Pharmacologic Actions |
Mental Disorders Autonomic Agents Therapeutic Uses Norepinephrine Vasoconstrictor Agents Peripheral Nervous System Agents Antisocial Personality Disorder Personality Disorders |