This proposal evaluates the safety and effectiveness of a noradrenergic drug named atomoxetine combined with motor training to enhance cortical plasticity and improve hand function after stroke.

Extensive studies in laboratory animals and humans over the last ten years indicate that some medications, especially amphetamine, given with specific physical therapy may improve motor learning (and therefore recovery from stroke) more than physical therapy alone. However, the number of patients in clinical trials who have received physical therapy and amphetamine is very small, for two reasons: because amphetamine may interact with many other medications that stroke patients are already taking, and because its potential for addiction precludes its use on a daily basis. The investigators now wish to evaluate the effectiveness of a more selective medication, atomoxetine, known to have many fewer side effects and no potential for drug addiction. The proposed mechanism by which amphetamine enhances recovery is by increasing central levels of norepinephrine. While the investigators already know that this drug is more selective than amphetamine, the investigators would like to evaluate its effects on hand motor learning and motor recovery in chronic stroke patients in a clinical setting.

Inclusion Criteria:

• Chronic stroke patients
• Single stroke
• Chronic (more than 6 months after from stroke)
• At least 21 years old, but there is no upper age range for this project.
• Participants NOT able to extend the affected metacarpophalangeal joints at least 10° and the wrist 20°.

Exclusion Criteria:

• History of head injury with loss of consciousness
• History of severe alcohol or drug abuse
• History of psychiatric illness
• Unstable cardiac dysrhythmia
• High blood pressure (systolic pressure >160 mm Hg and/or diastolic pressure >100 mm Hg)
• History of myocardial infarction or unstable angina
• Pregnancy
• Glaucoma, history of hypersensitivity or idiosyncrasy to sympathomimetic drugs.
• Subjects using drugs suspected of interfering with plasticity, such as MAOI, alpha-adrenergic antagonists, benzodiazepines, muscarinic receptor antagonists, dopaminergic antagonists, or other neuroleptics within 3 months of recruitment.