Exploring Learning and Unlearning of Fear

Study Overview
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Brief Summary
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The present study investigates the effect of d-cycloserine on learning and unlearning of fear in healthy humans and its underlying effect on the amygdala. As a second objective, the effect of genotype on fear learning will be studied.

Detailed Description
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A growing body of evidence suggests that the extinction of fear is mediated by the N-methyl-D-aspartate (NMDA) receptor activity in the basolateral amygdala. Intra-amygdala infusions of antagonists of this glutamate receptor in small animals (eg: rats, mice) have demonstrated a blockage of fear acquisition and extinction. Agonists, on the other hand, facilitate conditioned fear extinction. The animal studies are all based on the simple fear learning paradigm of conditioning. However, it is not clear that human anxiety disorders are based on prior conditioning encounter. Therefore it is important to disentangle the effect of DCS on acquisition and extinction in the context of a simple learning paradigm, particular its effect on the human amygdala.

Official Title
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The Effect of D-cycloserine on Fear Learning and Extinction

Conditions
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Healthy Individuals

Intervention / Treatment
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* Drug: d-Cycloserine
* Drug: Lactose pill
* Genetic: Saliva sample
* Other: Functional neuroimaging (fMRI)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: No axis I diagnosis compatible with the DSM-IV by means of a structured diagnostic interview Right-handed Exclusion Criteria: Current psychopharmacological or psychological treatment. The presence of a physical/medical condition that may interfere with the study. A contraindication for the use of DCS Pacemaker, medication pump (such as insulin pump), hearing aid, removable prosthodontics Metal in or on body (such as acupuncture needles, artificial limbs, stents, metal splints, clips, implanted electrodes, tattoos, or piercings)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: d-Cycloserine Acquisition<br>d-Cycloserine will be given on day1, before acquisition | Drug: d-Cycloserine<br>* 250mg, one dose, 2hrs prior to fMRI<br>* Other names: Cycloserine, King Pharmaceuticals Ltd;Genetic: Saliva sample<br>* Buccal cell material will be sampled from all participants on day3<br>* Other names: Whatman's Sterile Omni Swabs (www.whatman.com);Other: Functional neuroimaging (fMRI)<br> <br> |
| Active Comparator: d-Cycloserine Extinction<br>d-Cycloserine will be administered on day2, before extinction | Drug: d-Cycloserine<br>* 250mg, one dose, 2hrs prior to fMRI<br>* Other names: Cycloserine, King Pharmaceuticals Ltd;Genetic: Saliva sample<br>* Buccal cell material will be sampled from all participants on day3<br>* Other names: Whatman's Sterile Omni Swabs (www.whatman.com);Other: Functional neuroimaging (fMRI)<br> <br> |
| Placebo Comparator: Placebo<br>A placebo pill will be administered on day1 and 2 | Drug: Lactose pill<br>* one dose, 2hrs prior to fmri<br>Genetic: Saliva sample<br>* Buccal cell material will be sampled from all participants on day3<br>* Other names: Whatman's Sterile Omni Swabs (www.whatman.com);Other: Functional neuroimaging (fMRI)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in BOLD-signal during a fear conditioning task | Subjects will participate in a 3-day experiment. Day1 (t0): Acquisition Day2 (T+24): extinction Day3 (T+48): re-exposure | t0, t+24, t+48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fear, Cycloserine, Conditioning, Functional neuroimaging, Anxiety disorders