Project Identifier: BNL-95-249B
Project Title:
Imaging the Dopamine Presynaptic Neuron with 11-C-Methylphenidate (4 injections)
Principle Investigator:
Dr. Joanna S. Fowler
Project started in: 1995
Project Funding Information:
Project received funding in Fiscal Year 1995.
Project used human subjects in Fiscal Year 1995.
Funding Sources:
DA 09490
Total Funding: $216,000
Project does not involve use of multiple protocols/subprojects.
IRB Review:
Type of Review: Full Board
Most Recent Approval: August 02, 1995
Number of Human Subjects in the Last Reporting Period for this Project: 10
(Reporting periods vary.)
Type of Human Subjects Involvement:
Internal administration of radioactive substances to human subjects.
Cocaine and methylphenidate (MP) are both psychostimulant drugs. Yet cocaine is considered one of the most reinforcing and addictive drugs of abuse, while MP is widely used to treat attention deficit disorder in children. MP has a similar affinity for the dopamine transporter (DAT) as cocaine. We propose to use positron emission tomography (PET) in conjunction with 11-C-methylphenidate to measure brain pharmacokinetics of MP; d-threo methylphenidate, to measure DAT occupancy after single and repeated intravenous (iv) MP administration, and 11-C-cocaine to evaluate binding inhibition by pharmacological doses of MP. We propose to study 25 subjects each year for three years. Each subject will receive four PET scans over a period of 3-4 weeks. The subjects have a short-lived positron emitter tracer administered and are subsequently scanned with positron emission tomography (PET).
A potential side effect of radiation is the induction of cancer. However, no harm in a human individual or in a large population exposed at doses as low as those delivered in this procedure has been reported. The estimation of risk of harm can be obtained only by extrapolation from much higher doses. Methylphenidate is a mild central nervous system stimulant used to treat attention deficit disorder and narcolepsy. It increases heart rate and blood pressure and can cause a behavioral high. It can also elicit negative feelings of anxiety. In the event that either cardiovascular or behavioral complications occur, they can be effectively treated with an intramuscular injection of a neuroleptic. Since methylphenidate will be administered intravenously, the likelihood of cardiac stimulation is higher. There is also some evidence that methylphenidate may lower the seizure threshold in some individuals with no history of seizure disorders. Therefore, methylphendiate should not be given to patients with cardiac disease or patients with a past history of seizure disorders. Arterial catheterization has the following rare but possible complications: pain during placement of the catheter, a risk of bleeding at the skin puncture site, the possibility of local infection and temporary or permanent impairment of the blood supply to portions of the hand. Whenever blood is removed or a substance injected by venipuncture, there is minor discomfort and a slight possibility of local bleeding in the tissues.