The Influence of Glutamate on Memory in Humans

Study Overview
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Brief Summary
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The hippocampus is particularly laden with n-methyl-d-aspartate (NMDA) receptors, and is at the same time one of the most important sites in declarative memory. The rationale of this study is that the NMDA partial agonist D-Cycloserine will promote learning compared to a placebo. On the other hand, the NMDA receptor antagonist Memantine might lead to reduced memory. We believe that the influence of NMDA receptors on memory can be determined via acute co-activation of the NMDA receptors with Cycloserine® (King Pharmaceuticals Ltd, active ingredient: DCycloserin, dose: 250 mg) and Memantine (Axura®, Merz, active ingredient: Memantine, dose: 20 mg)on both a behavioral and functional (fMRI) level.

Official Title
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The NMDA Receptor Co-agonist D-cycloserine Accelerates Associative Learning in the Human Hippocampal CA Region

Conditions
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Healthy Individuals

Intervention / Treatment
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* Drug: Sugar pill
* Drug: Sugar pill
* Drug: Sugar pill
* Drug: Sugar pill
* Drug: Glutamic Acid
* Drug: Glutamic Acid
* Drug: Memantine
* Drug: Memantine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: German native language or native language level Able to give written informed consent right-handed Exclusion Criteria: inability to give written informed consent, underaged minors, contractually incapable persons, persons in legal custody any psychiatric, neurological or internal illness hematoporphyria (enzyme sickness) intake of medication (except oral contraceptives) simultaneous participation in other clinical studies hypersensitivity to Memantine or other anti-dementia substances, or to D-Cycloserine alcohol abuse epilepsy depression serious anxiety or psychosis serious kidney insufficiency intake of Ethionamide or Isoniazide pregnancy or women who are nursing liver or kidney problems intake of NMDA-antagonists, such as Amantadine, Ketamine, or Dextromethorphan vegetarians stomach ulcer, if treated with medication renal tubular acidosis urinary infections (with proteus bacteria) recent heart attack, heart failure, or uncontrolled high blood pressure intake of L-Dopa, dopaminergic agonists, and anticholinergics intake of barbiturates, spasmolytics, Phenytoin, Amantadine, oral coagulators, warfarin, HCT (Hydrochlorothiazide) heart or cranial operations 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) claustrophobia

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 35 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 |
| --- | --- |
| Placebo Comparator: Sugar pill, behavioral glutamic acid<br>Placebo condition for D-Cycloserine | Drug: Sugar pill<br>* 250 mg, one dose, 60 min prior<br>* Other names: Placebo condition for D-Cycloserine, behavioral study;|
| Placebo Comparator: Sugar pill, fMRI, glutamic acid<br>Placebo condition for D-Cycloserine, fMRI | Drug: Sugar pill<br>* 250 mg, one dose, 60 min prior<br>* Other names: Placebo condition for D-Cycloserine, fMRI;|
| Placebo Comparator: Sugar pill, memantine, behavioral<br>Placebo condition Memantine, behavioral | Drug: Sugar pill<br>* 20 mg, one dose, 8 hours prior<br>* Other names: Placebo condition Memantine, behavioral;|
| Placebo Comparator: Sugar pill, memantine, fMRI<br>Placebo condition Memantine, fMRI | Drug: Sugar pill<br>* 20 mg, one dose, 8 hours prior<br>* Other names: Placebo condition Memantine, fMRI;|
| Active Comparator: D-Cycloserine behavioral<br> | Drug: Glutamic Acid<br>* 250 mg, one dose, 60 minutes prior<br>* Other names: D-Cycloserine, King Pharmaceuticals;|
| Active Comparator: D-Cycloserine, fMRI<br> | Drug: Glutamic Acid<br>* 250 mg, one dose, 60 minutes prior<br>* Other names: D-Cycloserine, King Pharmaceuticals;|
| Active Comparator: Memantine, behavioral<br> | Drug: Memantine<br>* 20 mg, one dose, 8 hours prior<br>* Other names: Axura, Merz;|
| Active Comparator: Memantine, fMRI<br> | Drug: Memantine<br>* 20 mg, one dose, 8 hours prior<br>* Other names: Axura, Merz;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| fMRI during learning task |  | once at drug administration |